Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Adenylate Cyclase Toxin: One of the virulence factors produced by virulent BORDETELLA organisms. It is a bifunctional protein with both ADENYLYL CYCLASES and hemolysin components.Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3.Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Guanylyl Imidodiphosphate: A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Pituitary Adenylate Cyclase-Activating Polypeptide: A multi-function neuropeptide that acts throughout the body by elevating intracellular cyclic AMP level via its interaction with PACAP RECEPTORS. Although first isolated from hypothalamic extracts and named for its action on the pituitary, it is widely distributed in the central and peripheral nervous systems. PACAP is important in the control of endocrine and homeostatic processes, such as secretion of pituitary and gut hormones and food intake.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.Fluorides: Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Cholera Toxin: An ENTEROTOXIN from VIBRIO CHOLERAE. It consists of two major protomers, the heavy (H) or A subunit and the B protomer which consists of 5 light (L) or B subunits. The catalytic A subunit is proteolytically cleaved into fragments A1 and A2. The A1 fragment is a MONO(ADP-RIBOSE) TRANSFERASE. The B protomer binds cholera toxin to intestinal epithelial cells, and facilitates the uptake of the A1 fragment. The A1 catalyzed transfer of ADP-RIBOSE to the alpha subunits of heterotrimeric G PROTEINS activates the production of CYCLIC AMP. Increased levels of cyclic AMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells.Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Receptors, Adrenergic, beta: One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Bordetella pertussis: A species of gram-negative, aerobic bacteria that is the causative agent of WHOOPING COUGH. Its cells are minute coccobacilli that are surrounded by a slime sheath.Alprostadil: A potent vasodilator agent that increases peripheral blood flow.Pertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Kinetics: The rate dynamics in chemical or physical systems.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.Guanine NucleotidesReceptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.1-Methyl-3-isobutylxanthine: A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASESThionucleotides: Nucleotides in which the base moiety is substituted with one or more sulfur atoms.Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to DIDANOSINE (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite.Vasoactive Intestinal Peptide: A highly basic, 28 amino acid neuropeptide released from intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems and is neuroprotective. It binds special receptors (RECEPTORS, VASOACTIVE INTESTINAL PEPTIDE).Glucagon: A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type IPhenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.Diterpenes: Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate.Iodocyanopindolol: A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.Turkeys: Large woodland game BIRDS in the subfamily Meleagridinae, family Phasianidae, order GALLIFORMES. Formerly they were considered a distinct family, Melegrididae.3',5'-Cyclic-AMP Phosphodiesterases: Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.Dihydroalprenolol: Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with LIDOCAINE injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring.Receptors, Pituitary Hormone: Cell surface proteins that bind pituitary hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Since many pituitary hormones are also released by neurons as neurotransmitters, these receptors are also found in the nervous system.Pindolol: A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Benzyl Alcohols: Alcohols derived from the aryl radical (C6H5CH2-) and defined by C6H5CHOH. The concept includes derivatives with any substituents on the benzene ring.8-Bromo Cyclic Adenosine Monophosphate: A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Neuropeptides: Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.Cyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Bucladesine: A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Alprenolol: One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.Receptors, Vasoactive Intestinal Peptide: Cell surface proteins that bind VASOACTIVE INTESTINAL PEPTIDE; (VIP); with high affinity and trigger intracellular changes which influence the behavior of cells.Receptors, Purinergic: Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Phosphoric Diester Hydrolases: A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone: Inhibitor of phosphodiesterases.Fluphenazine: A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE.Stimulation, Chemical: The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.Nucleoside Diphosphate SugarsSignal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Manganese: A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)GTP-Binding Protein alpha Subunits, Gs: A family of heterotrimeric GTP-binding protein alpha subunits that activate ADENYLYL CYCLASES.Erythrocyte Membrane: The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.IminesAdenine NucleotidesReceptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Phosphotransferases: A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.Trifluoperazine: A phenothiazine with actions similar to CHLORPROMAZINE. It is used as an antipsychotic and an antiemetic.Molecular Weight: The sum of the weight of all the atoms in a molecule.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.ADP-ribosyl Cyclase: A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of EPOPROSTENOL, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation.Hybrid Cells: Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide: A family of G-protein-coupled receptors that share significant homology with GLUCAGON RECEPTORS. They bind PITUITARY ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE with high affinity and trigger intracellular changes that influence the behavior of CELLS.Enkephalin, Leucine-2-Alanine: A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.Vasopressins: Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.Adenosine Diphosphate Sugars: Esters formed between the aldehydic carbon of sugars and the terminal phosphate of adenosine diphosphate.Leydig Cell Tumor: Gonadal interstitial or stromal cell neoplasm composed of only LEYDIG CELLS. These tumors may produce one or more of the steroid hormones such as ANDROGENS; ESTROGENS; and CORTICOSTEROIDS. Clinical symptoms include testicular swelling, GYNECOMASTIA, sexual precocity in children, or virilization (VIRILISM) in females.Receptors, Prostaglandin: Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Lypressin: The porcine antidiuretic hormone (VASOPRESSINS). It is a cyclic nonapeptide that differs from ARG-VASOPRESSIN by one amino acid, containing a LYSINE at residue 8 instead of an ARGININE. Lys-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.GTP Phosphohydrolases: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Somatostatin: A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.Parathyroid Hormone: A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Bacterial Toxins: Toxic substances formed in or elaborated by bacteria; they are usually proteins with high molecular weight and antigenicity; some are used as antibiotics and some to skin test for the presence of or susceptibility to certain diseases.Receptors, Vasoactive Intestinal Peptide, Type II: A pituitary adenylate cyclase-activating peptide receptor subtype found in LYMPHOCYTES. It binds both PACAP and VASOACTIVE INTESTINAL PEPTIDE and regulates immune responses.Receptors, Muscarinic: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Receptors, Gastrointestinal Hormone: Cell surface proteins that bind gastrointestinal hormones with high affinity and trigger intracellular changes influencing the behavior of cells. Most gastrointestinal hormones also act as neurotransmitters so these receptors are also present in the central and peripheral nervous systems.Toxins, Biological: Specific, characterizable, poisonous chemicals, often PROTEINS, with specific biological properties, including immunogenicity, produced by microbes, higher plants (PLANTS, TOXIC), or ANIMALS.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Secretin: A peptide hormone of about 27 amino acids from the duodenal mucosa that activates pancreatic secretion and lowers the blood sugar level. (USAN and the USP Dictionary of Drug Names, 1994, p597)Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Receptors, Cyclic AMP: Cell surface proteins that bind cyclic AMP with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized cyclic AMP receptors are those of the slime mold Dictyostelium discoideum. The transcription regulator CYCLIC AMP RECEPTOR PROTEIN of prokaryotes is not included nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Receptors, Dopamine: Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Azides: Organic or inorganic compounds that contain the -N3 group.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Receptors, Guanylate Cyclase-Coupled: A class of cellular membrane receptors that either have an intrinsic guanylate cyclase activity or are closely coupled to specific guanylate cyclases within the cell.Peptide PHI: A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exact amino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is found in the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.Receptors, Vasoactive Intestinal Polypeptide, Type I: A pituitary adenylate cyclase-activating polypeptide receptor subtype that binds both PACAP and VASOACTIVE INTESTINAL PEPTIDE. It is found predominately in the BRAIN.Oxotremorine: A non-hydrolyzed muscarinic agonist used as a research tool.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.Receptors, Parathyroid Hormone: Cell surface proteins that bind PARATHYROID HORMONE with high affinity and trigger intracellular changes which influence the behavior of cells. Parathyroid hormone receptors on BONE; KIDNEY; and gastrointestinal cells mediate the hormone's role in calcium and phosphate homeostasis.Receptors, Epoprostenol: Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Receptors, Atrial Natriuretic Factor: Cell surface proteins that bind ATRIAL NATRIURETIC FACTOR with high affinity and trigger intracellular changes influencing the behavior of cells. They contain intrinsic guanylyl cyclase activity.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Receptors, Glucagon: Cell surface receptors that bind glucagon with high affinity and trigger intracellular changes which influence the behavior of cells. Activation of glucagon receptors causes a variety of effects; the best understood is the initiation of a complex enzymatic cascade in the liver which ultimately increases the availability of glucose to body organs.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Pseudohypoparathyroidism: A hereditary syndrome clinically similar to HYPOPARATHYROIDISM. It is characterized by HYPOCALCEMIA; HYPERPHOSPHATEMIA; and associated skeletal development impairment and caused by failure of response to PARATHYROID HORMONE rather than deficiencies. A severe form with resistance to multiple hormones is referred to as Type 1a and is associated with maternal mutant allele of the ALPHA CHAIN OF STIMULATORY G PROTEIN.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.OxadiazolesSolubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Thyrotropin: A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.Receptors, Histamine H2: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Arginine Vasopressin: The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.QuinoxalinesProtein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Thyroid Gland: A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively.Ribose: A pentose active in biological systems usually in its D-form.Dithiothreitol: A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Receptors, Prostaglandin E: Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.NAD: A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Nucleotides, Cyclic2-Chloroadenosine: 2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.Intestinal Secretions: Fluids originating from the epithelial lining of the intestines, adjoining exocrine glands and from organs such as the liver, which empty into the cavity of the intestines.Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).GTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.AMP Deaminase: An enzyme that catalyzes the deamination of AMP to IMP. EC 3.5.4.6.Dictyostelium: A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.Pituitary Gland, Anterior: The anterior glandular lobe of the pituitary gland, also known as the adenohypophysis. It secretes the ADENOHYPOPHYSEAL HORMONES that regulate vital functions such as GROWTH; METABOLISM; and REPRODUCTION.Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Trypsin: A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

Cell polarization: chemotaxis gets CRACKing. (1/5304)

An early stage in the establishment of cell polarity during chemotaxis of Dictyostelium dicoideum has been identified by a recent study; the new results also show that the development of cell polarity does not rely upon cytoskeletal rearrangement, and may use a spatial sensing mechanism.  (+info)

Probing the function of Bordetella bronchiseptica adenylate cyclase toxin by manipulating host immunity. (2/5304)

We have examined the role of adenylate cyclase-hemolysin (CyaA) by constructing an in-frame deletion in the Bordetella bronchiseptica cyaA structural gene and comparing wild-type and cyaA deletion strains in natural host infection models. Both the wild-type strain RB50 and its adenylate cyclase toxin deletion (DeltacyaA) derivative efficiently establish persistent infections in rabbits, rats, and mice following low-dose inoculation. In contrast, an inoculation protocol that seeds the lower respiratory tract revealed significant differences in bacterial numbers and in polymorphonuclear neutrophil recruitment in the lungs from days 5 to 12 postinoculation. We next explored the effects of disarming specific aspects of the immune system on the relative phenotypes of wild-type and DeltacyaA bacteria. SCID, SCID-beige, or RAG-1(-/-) mice succumbed to lethal systemic infection following high- or low-dose intranasal inoculation with the wild-type strain but not the DeltacyaA mutant. Mice rendered neutropenic by treatment with cyclophosphamide or by knockout mutation in the granulocyte colony-stimulating factor locus were highly susceptible to lethal infection by either wild-type or DeltacyaA strains. These results reveal the significant role played by neutrophils early in B. bronchiseptica infection and by acquired immunity at later time points and suggest that phagocytic cells are a primary in vivo target of the Bordetella adenylate cyclase toxin.  (+info)

Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes. (3/5304)

BACKGROUND: In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C beta-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure. METHODS AND RESULTS: A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation. CONCLUSIONS: Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized beta-adrenergic receptor signaling.  (+info)

Kinetic analysis of drug-receptor interactions of long-acting beta2 sympathomimetics in isolated receptor membranes: evidence against prolonged effects of salmeterol and formoterol on receptor-coupled adenylyl cyclase. (4/5304)

The long-acting beta2 sympathomimetics salmeterol and formoterol have been presumed to exert their prolonged action either by binding to an accessory binding site ("exo-site") near the beta2 adrenoceptor or by their high affinity for beta2 adrenoceptors and correspondingly slow dissociation. Whereas most studies with salmeterol had been done in intact tissues, which have slow diffusion and compartmentation of drugs in lipophilic phases, that restrict drug access to the receptor biophase, we used purified receptor membranes from rat lung and disaggregated calf tracheal myocytes as model systems. Binding experiments were designed to measure the slow dissociation of agonists by means of delayed association of (-)-[125I]iodopindolol. Rat lung membranes were pretreated with high concentrations of agonists (salmeterol, formoterol, isoprenaline) before dissociation was induced by 50-fold dilution. Half-times of association of (-)-[125I]iodopindolol remained unchanged compared with untreated controls, indicating that dissociation of agonists occurred in less than 2 min. Adenylyl cyclase experiments were designed to determine the on and off kinetics of agonists to beta2 adrenoceptors by measuring the rate of receptor-induced cyclic AMP (cAMP) formation. Experiments were performed in tracheal membranes characterized by high Vmax values of cAMP formation. Adenylyl cyclase activation occurred simultaneously with the addition of the agonist, continued linearly with time for 60 min, and ceased immediately after the antagonist was added. Similarly, when receptor membranes were preincubated in a small volume with high salmeterol concentrations, there was a linear increase in cAMP formation, which was immediately interrupted by a 100-fold dilution of the reaction mixture. This militates against the exo-site hypothesis. On the other hand, dissociation by dilution was much less when membranes were preincubated with a large volume of salmeterol at the same concentration, indicating that physicochemical effects, and not exo-site binding, underlie its prolonged mode of action.  (+info)

Biochemical and cytochemical studies on adenylate cyclase activity in the developing rat submandibular gland: differentiation of of the acinar secretory compartment. (5/5304)

To investigate membrane changes in development of the exocrine cells of the rat submandibular gland (SMG), biochemical and cytochemical studies of adenylate cyclase activity were performed on prenatal and postnatal glands. SMG rudiments and glands were studied from 15 days of gestation op to birth and 1, 2, 3, 4 and 24 weeks after birth. Glands were chemically assayed for adenylate cyclase activity using the procedures of Salomon and coworkers and cytochemically studied using a procedure which was verified biochemically. At 15-16 days of gestation basal adenylate cyclase activity was low and no staining could be observed. Adenylate cyclase activity rose six-fold from the 16th to the 18th day of gestation. Adenylate cyclase staining became evident along the surface of most of the cells of the rudiment at this time. Basal adenylate cyclase activity remained relatively constant from the 18th day of gestation up to 24 weeks of age. However, sequential changes were seen in the cytochemical localization, especially in relation to the apical plasma membrane of the developing secretory cells.  (+info)

Facilitation of signal onset and termination by adenylyl cyclase. (6/5304)

The alpha subunit (Gsalpha) of the stimulatory heterotrimeric guanosine triphosphate binding protein (G protein) Gs activates all isoforms of mammalian adenylyl cyclase. Adenylyl cyclase (Type V) and its subdomains, which interact with Gsalpha, promoted inactivation of the G protein by increasing its guanosine triphosphatase (GTPase) activity. Adenylyl cyclase and its subdomains also augmented the receptor-mediated activation of heterotrimeric Gs and thereby facilitated the rapid onset of signaling. These findings demonstrate that adenylyl cyclase functions as a GTPase activating protein (GAP) for the monomeric Gsalpha and enhances the GTP/GDP exchange factor (GEF) activity of receptors.  (+info)

The 5'-flanking region of the mouse adenylyl cyclase type VIII gene imparts tissue-specific expression in transgenic mice. (7/5304)

The calcium-stimulated adenylyl cyclases (ACs) play a central role in stimulus-dependent modification of synaptic function. The type VIII AC (AC8) is one of three mammalian calcium-stimulated isoforms, each of which is expressed in a region-specific manner in the CNS. To delineate the DNA sequences responsible for appropriate targeting of AC8 expression, we report here the complete structure of the AC8 gene and define the pattern of expression of the full-length cDNA and its splice variants. In addition to expression within the brain, robust expression of AC8 was also found in the lung. By in situ hybridization, we have found the highest expression of AC8 mRNA within the olfactory bulb, thalamus, habenula, cerebral cortex, and hypothalamic supraoptic and paraventricular nuclei. By generating transgenic mice whose expression of beta-galactosidase is controlled by the AC8 5'-flanking DNA sequences, we demonstrate that the DNA sequences within the 10 kb preceding exon 1 are critical for establishment of this region-specific pattern. This spectrum of sites of production is unique to AC8 among the calcium-stimulated adenylyl cyclases and suggests nonredundant functions with other adenylyl cyclases in neuroendocrine regulation and/or behavior.  (+info)

Role of protein kinase A in the maintenance of inflammatory pain. (8/5304)

Although the initiation of inflammatory pain (hyperalgesia) has been demonstrated to require the cAMP second messenger signaling cascade, whether this mechanism and/or other mechanisms underlie the continued maintenance of the induced hyperalgesia is unknown. We report that injection of adenylyl cyclase inhibitors before but not after injection of direct-acting hyperalgesic agents (prostaglandin E2 and purine and serotonin receptor agonists) resulted in reduction in hyperalgesia, evaluated by the Randall-Selitto paw-withdrawal test. In contrast, injection of protein kinase A (PKA) inhibitors either before or after these hyperalgesic agents resulted in reduced hyperalgesia, suggesting that hyperalgesia after its activation was maintained by persistent PKA activity but not by adenylyl cyclase activity. To evaluate further the role of PKA activity in the maintenance of hyperalgesia, we injected the catalytic subunit of PKA (PKACS) that resulted in hyperalgesia similar in magnitude to that induced by the direct-acting hyperalgesic agents but much longer in duration (>48 vs 2 hr). Injection of WIPTIDE (a PKA inhibitor) at 24 hr after PKACS reduced hyperalgesia, suggesting that PKACS hyperalgesia is not independently maintained by steps downstream from PKA. In summary, our results indicate that, once established, inflammatory mediator-induced hyperalgesia is no longer maintained by adenylyl cyclase activity but rather is dependent on ongoing PKA activity. An understanding of the mechanism maintaining hyperalgesia may provide important insight into targets for the treatment of persistent pain.  (+info)

Inositol phosphate accumulation and adenylate cyclase activity were investigated in the cortex of young and aged ethanol-treated rats. Three months of ethanol treatment of young rats decreased maximal stimulation of inositol phosphate accumulation by carbachol by 26%, from 494 ± 76% of basal turnover in control animals to 396 ± 54% in ethanol-treated animals (mean ± SD). In aged rats ethanol-related changes were no longer observed but age-related changes were evident. EC50 was significantly higher than in young animals and maximal stimulation was significantly lower. Basal adenylate cyclase activity in cortical membranes of all groups of animals was not different. Forskolin-stimulated adenylate cyclase activity was not affected by ethanol treatment, but was higher in aged animals. The activity of forskolin-stimulated adenylate cyclase in the presence of carbachol was higher in both young and aged ethanol-treated animals, when compared to young controls. These results suggest that both ethanol ...
The effects of Ca2+-calmodulin on adenylate cyclase activity in EGTA-washed, 27000 g particulate fractions of mouse and rat pancreatic islets were studied. Ca2+ (10 microM)-calmodulin (1 microM) stimulated adenylate cyclase activity 53.1 +/- 5.2 (N = 6)% in the particulate fraction of rat islets. Trifluoperazine (50 microM), a specific inhibitor of calmodulin, inhibited the Ca2+-calmodulin activation of the adenylate cyclase activity of this fraction of rat islets. These results confirm previous reports dealing with Ca2+-Calmodulin and rat islet adenylate cyclase [Valverde, Vandermeers. Anjaneyulu & Malaisse (1979) Science 206, 225-227; Sharp, Wiedenkeller, Kaelin, Siegel & Wollheim (1980) Diabetes 29, 74-77]. In contrast, however, Ca2+ (1-100 microM)-calmodulin (1-10 microM) did not stimulate the adenylate cyclase activity in the EGTA-washed particulate fraction of mouse islets, and trifluoperazine (50 microM) did not inhibit the adenylate cyclase activity of this fraction of mouse islets, ...
1. Sepharose 6B gel-filtration analysis of soluble adenylate cyclase from bovine corpus luteum is described. Both zonal and frontal techniques of analysis were used. 2. Under conditions of zonal analysis recoveries of activity were low. It was concluded that dissociation of two or more components of the adenylate cyclase complex was occurring on the column and that the maintenance of the complex was essential for the high-activity state of the catalytic unit. Two peaks of adenylate cyclase activity, of approximate mol. wts. 45,000 and 160,000 were detected. 3. The theory of frontal analysis (or steady-state gel filtration), applied to the study of the interacting components of the adenylate cyclase complex is discussed, and activity profiles are predicted. Activity profiles obtained experimentally be frontal analysis compared well with the theoretically predicted profile and provide evidence that dissociation of a high-activity complex, with concomitant loss of activity, does occur. Recoveries ...
TY - JOUR. T1 - Hormone-sensitive adenylate cyclase in glomerular cells. Possible role for inflammatory diseases of the glomerulus. AU - Paietta, Elisabeth M.. AU - Schwarzmeier, J. D.. AU - Simbruner, G.. AU - Latzka, U.. AU - Lubec, G.. PY - 1981. Y1 - 1981. N2 - Using the adenylate cyclase assay after Ross the authors examined hormone sensitivity of isolated glomerular cells. cAMP production was increased 1.3-1.6-fold by stimulation with isoproterenol, 1.5-1.8 times by prostaglandin E 1 and 1.4-1.5 times by histamine. The isoproterenol reaction could be completely inhibited by propranolol, the histamine effect was abolished by the H2-blocking agent cimetidine. As a control the authors applied sodium fluoride, which directly activates the catalytic adenylate cyclase unit, increasing the activity 1.8-2.7 times (depending on the method of homogenization). These findings could reflect some physiological or pathophysiological implications, which are discussed.. AB - Using the adenylate cyclase ...
A factor [the feedback regulator (FR)] formed by adipocytes after the stimulation of a cAMP raising hormone has been found to be a potent inhibitor of membrane-bound adenylate cyclase [EC 4.6.1.1.; ATP pyrophosphate-lyase (cyclizing)]. In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate cyclase by lowering the Vmax without affecting the apparent Km for ATP (0.3-0.6 mM). The apparent Ka for epinephrine (5-6 muM) was also not affected by FR. The inhibitory action of FR was partially countered by Mg2+ ions. An increase in phosphorylation of plasma membrane was observed when FR was present in the incubation system. The concentration required for a 50% inhibition was four times higher when adenosine 5-(beta,gamma-imino) triphosphate [AMP-P(NH)P] replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused by FR. Increase in FR inhibition obtained by adding low ...
TY - JOUR. T1 - Multiple forms of brain adenylate cyclase. T2 - Stimulation by Mn2+. AU - Malamuda, Daniel F.. AU - DiRusso, Concetta C.. AU - Aprille, June R.. PY - 1977/11/23. Y1 - 1977/11/23. N2 - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both solubilization and storage at 0-4°C, the ability of the enzyme to be stimulated by Mn2+ was maintained for up to one week. By including Mn+ in the assay of adenylate cyclase in gel fractions after isoelectric focusing, two distinct peaks of enzyme activity (pI1 = 5.8, pI2 = 6.4) were detected, suggesting the existence of more than one type of catalytic subunit in mouse brain cell membranes.. AB - Mn2+-stimulated adenylate cyclase (ATP pyrophosphate-lyase-(cyclizing), EC 4.6.1.1) activity in detergent solubilized preparations from mouse brain. While NaF-stimulated activity was decreased by both ...
Adenylyl Cyclase Type V Inhibitor, NKY80 - CAS 299442-43-6 - Calbiochem The Adenylyl Cyclase Type V Inhibitor, NKY80, also referenced under CAS 299442-43-6, controls the biological activity of Adenylyl Cyclase Type V. This small molecule/inhibitor is primarily used for Cell Signaling applications. - Find MSDS or SDS, a COA, data sheets and more information.
Aiba H.. The regulatory region of the Escherichia coli cya gene was analyzed by using S1 nuclease mapping and in vitro transcription experiments. The cya gene was transcribed, both in vivo and in vitro, from one major promoter (P2) and two weak promoters (P1 and P1) that are located about 200 base pairs upstream of P2. The transcription from P2 was specifically inhibited by cAMP-CRP (cAMP receptor protein) in vitro. This regulatory mechanism was shown to be physiologically relevant through quantitative analyses of the cya mRNA in intact cells by S1 and dot blot assays. DNase I protection experiments revealed that cAMP-CRP binds to the cya DNA region between +11 and -20, in which a consensus CRP binding sequence is present. Moreover, it was found that cAMP-CRP alters the binding of RNA polymerase to the promoter region, thus inhibiting the transcription of the cya gene.. J. Biol. Chem. 260:3063-3070(1985) [PubMed] [Europe PMC] ...
An important eukaryotic signal transduction pathway involves the regulation of the effector enzyme adenylate cyclase, which produces the second messenger, cAMP. Previous genetic analyses demonstrated that glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene requires the function of adenylate cyclase, encoded by the git2 gene. As mutations in git2 and in six additional git genes are suppressed by exogenous cAMP, these upstream git genes were proposed to act to produce a glucose-induced cAMP signal. We report here that assays of cAMP levels in wild-type and various mutant S. pombe cells, before and after exposure to glucose, show that this is the case. The data suggest that the cAMP signal results from the activation of adenylate cyclase. Therefore these upstream git genes appear to encode a glucose-induced adenylate cyclase activation pathway. Assays of cAMP on a strain carrying a mutation in the git6 gene, which acts downstream of adenylate cyclase, indicate that ...
We next investigated whether beta gamma subunits play a role in the sensitization of type VI adenylyl cyclase activity; using expression of alpha tau to inhibit beta gamma-mediated effects, we found that the quinpirole-induced sensitization of type VI adenylyl cyclase was abolished ...
Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of obese and type 2 diabetic rats as affected by the intranasal insulin treatment Journal of Evolutionary Biochemistry and Physiology Pleiades Publishing 0022-0930 1608-3202 10.1134/S0022093014050044
H2O2 and oxygen-derived free radicals modulate vasodilator mechanisms.1 2 3 4 5 6 9 The present studies indicate that H2O2 enhances adenylyl cyclase activation and that the effect is dependent (in part) on the presence of iron and is blunted by agents that act to inhibit tyrosine kinase activity.. Our data suggest that the oxygen-derived species mediating the enhancement of adenylyl cyclase activation is either H2O2 itself or the hydroxyl radical. Incubation of cells with xanthine oxidase and purine resulted in a qualitatively similar enhancement of adenylyl cyclase activation. The effect of purine and xanthine oxidase was not blocked by coincubation with superoxide dismutase (which catalyzes the conversion from superoxide anion to H2O2). This suggests that the generation of the superoxide anion is not involved in the mechanism of enhancement of adenylyl cyclase activation. However, pretreatment with either catalase (which catalyzes conversion of H2O2 to water) or with deferoxamine (which ...
TY - JOUR. T1 - Demonstration and Characterization of Opiate Inhibition of the Striatal Adenylate Cyclase. AU - Law, P. Y.. AU - Wu, J.. AU - Koehler, J. E.. AU - Loh, H. H.. PY - 1981/5. Y1 - 1981/5. N2 - Abstract: The conditions in which Leu5‐enkephalin inhibition of striatal adenylate cyclase was observed were defined. It was determined that enkephalin inhibition was dependent on GTP. The apparent Km for GTP in opiate inhibition was determined to be 0.5 and 2 μM when 0.1 mM‐ and 0.5 mM‐ATP were used as substrate. ITP, but not CTP or UTP, could substitute for GTP in the reaction. Though the addition of monovalent cations-Na+,K+, Li+, Cs+, and choline+-stimulated striatal adenylate cyclase activity, enkephalin inhibition of striatal adenylate cyclase did not require Na+ when theophylline was used as the phosphodiesterase inhibitor. Under optimal conditions, i.e., 20 μM‐GTP and 100 mM‐Na+, Leu5‐enkephalin inhibited the striatal adenylate cyclase activity by 23-27%. When the ...
Fingerprint Dive into the research topics of Effect of membrane phospholipid composition changes on adenylate cyclase activity in normal and rous-sarcoma-transformed chicken embryo fibroblasts. Together they form a unique fingerprint. ...
The parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a dominant-negative strategy, we found that reducing adenylate cyclase activity by about 50% allowed trypanosome growth but reduced the parasites ability to control the early innate immune defense of the host. Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. Thus, adenylate cyclase activity of lyzed trypanosomes favors early host colonization by live parasites. The role of adenylate cyclases at the host-parasite interface could explain the expansion and polymorphism of this gene family.. ...
This study investigates the hypothesis that inflammatory cytokines, interleukin (IL)-1alpha IL-1beta, and tumor necrosis factor (TNF), influence cardiac function by affecting calcium homeostasis and that this effect is mediated by the beta-adrenergic-adenylate cyclase system. After 4 days in culture, neonatal rat ventricular myocytes were treated with cytokines (10 ng/ml) for short (2 h) or longer (18 h) times. Myocyte calcium, contractility, and adenylate cyclase were measured under each condition. Anticipated stepwise increases in adenylate cyclase and intracellular calcium were found in controls (non-cytokine-treated) with 10(-7) M isoproterenol, 10(-7) M isoproterenol + 0.1 mM guanosine triphosphate, and 10(-9) M forskolin. Cells in the presence of cytokine for 2 h show increased basal calcium levels but no changes in adenylate cyclase activities, and isoproterenol fails to elevate adenylate cyclase levels or affect contractile shortening. After long-term treatment with IL-1beta or TNF, but ...
Adenylate cyclase activity of luteinized ovaries from gonadotropin-primed immature rats was stimulated by luteinizing hormone (LH), epinephrine and prostaglandin E1. Treatment of primed rats with human chorionic gonadotropin (hCG) caused a time-dependent loss of the adenylate cyclase response to LH, and the enzyme also became refractory to stimulation by epinephrine. Conversely, treatment of primed rats with epinephrine caused a time-dependent loss of the adenylate cyclase response to epinephrine, but the enzyme remained responsive to LH. The refractoriness of adenylate cyclase to epinephrine after desensitization by hCG or epinephrine was not reversed by Gpp(NH)p. These studies show that "cross-desensitization" of epinephrine-responsive adenylate cyclase activity in the ovary is induced by LH-receptor interaction, whereas β-adrenergic desensitization causes more specific refractoriness to epinephrine with no change in the LH receptor activation mechanism. This suggests the existence of ...
Soluble adenylyl cyclase can function in the nucleus, defining a nuclear microdomain of adenosine 3′,5′-monophosphate (cAMP) signaling. Bundey and Insel discuss the evidence for discrete signaling microdomains of cAMP, including the nucleus and caveolae, and conclude that such microdomains may be defined by the localized, subcellular expression of adenylyl cyclase isoforms.. ...
The interaction between RAS proteins and adenylyl cyclase was studied by using dominant interfering mutations of adenylyl cyclase from the yeast Saccharomyces cerevisiae. RAS proteins activate adenylyl cyclase in this organism. A plasmid expressing a catalytically inactive adenylyl cyclase was found to interfere dominantly with this activation. The interfering region mapped to the leucine-rich repeat region of adenylyl cyclase, which is homologous to domains present in several other proteins and is thought to participate in protein-protein interactions. ...
We have cloned a GC from Paramecium which has an N‐terminal P‐type ATPase‐like domain and a C‐terminal cyclase domain. So far, mammalian GC catalysts are either homodimers fused to an extracellular receptor by a single TM, or soluble heterodimers linked to a nitric oxide‐binding site (Schulz et al., 1991; Yu et al., 1996; Tang and Hurley, 1998; Koesling and Friebe, 1999). The ciliate GC domain differs. It has the unmistakable topology of a mammalian AC complete with catalytic C1a and C2a regions and two prominent membrane anchors, M1 and M2, with six TMs each. Therefore, the ciliate GC is not related to metazoan GCs but is a close relative of metazoan ACs. A striking difference between the ciliate GCs and their mammalian AC congeners was the switch of the C1a and C2a positions. The preference for GTP could be rationalized by looking at three amino acids which determine the nucleotide specifity in the catalytic pocket. In metazoan ACs, glutamine, lysine and aspartate define ATP as a ...
TY - JOUR. T1 - Hormonal stimulation of adenylyl cyclase through Gi-protein βγ subunits. AU - Federman, Alex D.. AU - Conklin, Bruce R.. AU - Schrader, Karen A.. AU - Reed, Randall R. AU - Bourne, Henry R.. PY - 1992/3/12. Y1 - 1992/3/12. N2 - AGONIST-BOUND receptors activate heterotrimeric (αβγ) G proteins by catalysing replacement by GTP of GDP bound to the α subunit, resulting in dissociation of γ-GTP from the βγ subunits. In most cases, α-GTP carries the signal to effectors, as in hormonal stimulation1-4 and inhibition5,6 of adenylyl cyclase by αs and αi respectively. By contrast, genetic evidence in yeast7 and studies in mammalian cells8-10 suggest that βγ subunits of G proteins may also regulate effector pathways. Indeed, of the four recombinant mammalian adenylyl cyclases available for study11-14, two, adenylyl cyclases II and IV, are stimulated by βγ . This effect of βγ requires costimulation by αs-GTP14,15. This conditional pattern of effector responsiveness led to ...
The myocardial potassium uptake during intracoronary isoproterenol stimulation was characterized in 12 anesthetized pigs. The beta-receptor subtype specificity and the effect of adenylate cyclase activation were determined. Potassium concentrations were continuously recorded by PVC-valinomycin minielectrodes in the left atrial cavity and in coronary sinus blood diverted through a shunt to the right atrium. The difference in potassium concentration between the left atrial cavity and coronary sinus, and the accumulated myocardial potassium uptake were calculated after computerized data sampling. By intracoronary drug infusion, changes in heart rate and systemic effects were minimized. Isoproterenol (0.6-0.8 microgram/min), a nonspecific beta-agonist, reduced coronary sinus potassium concentration transiently to a nadir of 0.28 (0.15-0.43) mM (median and 95% confidence interval) below control values (n = 12). The potassium uptake, which amounted to 140 (79-202) mumol/100 g tissue, corresponding to ...
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1CS4: COMPLEX OF GS-ALPHA WITH THE CATALYTIC DOMAINS OF MAMMALIAN ADENYLYL CYCLASE: COMPLEX WITH 2-DEOXY-ADENOSINE 3-MONOPHOSPHATE, PYROPHOSPHATE AND MG
Withdrawal of mice from chronic ethanol treatment results in a decreased responsiveness of striatal (but not mesolimbic) dopamine-sensitive adenylate cyclase activity to stimulation by dopamine. This subsensitivity is not apparent at the time of withdrawal from chronic feeding of ethanol, when animals are still intoxicated, but becomes evident as ethanol is eliminated from the animals. Addition of ethanol in vitro to tissue homogenates from ethanol-withdrawn animals, at concentrations similar to those found in brain at the time of withdrawal, normalizes the response of the adenylate cyclase to dopamine. No difference is evident between control and ethanol-withdrawn animals in stimulation of adenylate cyclase by sodium fluoride. The specificity of the response of striatal adenylate cyclase to stimulation by dopamine, as compared to other transmitters, is unaltered by chronic ethanol feeding. Chronic treatment with ethanol and withdrawal also does not affect the specific binding of spiroperidol in ...
RecName: Full=Adenylate cyclase type 6; EC=4.6.1.1;AltName: Full=Adenylate cyclase type VI;AltName: Full=ATP pyrophosphate-lyase 6;AltName: Full=Adenylyl cyclase 6;AltName: Full=Ca(2+)-inhibitable adenylyl ...
TY - JOUR. T1 - Differential unmasking of adenylate cyclase activity (AC) in cardiac membrane sheets and vesicles. AU - Fleming, J. W.. AU - Besch, H. R.. AU - Jones, L. R.. AU - Watanabe, A. M.. PY - 1978/1/1. Y1 - 1978/1/1. UR - http://www.scopus.com/inward/record.url?scp=0017841068&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0017841068&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:0017841068. VL - 20. JO - Pharmacologist. JF - Pharmacologist. SN - 0031-7004. IS - 3. ER - ...
In cultured intact LLC-PK1 renal epithelial cells, a nonhydrolyzable ATP analogue, ATP gamma S, inhibits AVP-stimulated cAMP formation. In LLC-PK1 membranes, several ATP analogues inhibit basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in a dose-dependent manner. The rank order potency of inhibition by ATP analogues suggests that a P2y type of ATP receptor is involved in this inhibition. The compound ATP gamma S inhibits agonist-stimulated adenylate cyclase activity in solubilized and in isobutylmethylxanthine (IBMX) and quinacrine pretreated membranes, suggesting that ATP gamma S inhibition occurs independent of AVP and A1 adenosine receptors and of phospholipase A2 activity. The ATP gamma S inhibition of AVP-stimulated adenylate cyclase activity is not affected by pertussis toxin but is attenuated by GDP beta S, suggesting a possible role for a pertussis toxin insensitive G protein in the inhibition. Exposure of intact LLC-PK cells to ATP gamma S results in a significant ...
Semantic Scholar extracted view of Spermine inhibition of basal and stimulated adenylate cyclase is mediated by the inhibitory GTP-binding protein (Gi). by Carlo Clô et al.
Adenylate cyclase type 5 (EC 4.6.1.1) (ATP pyrophosphate-lyase 5) (Adenylate cyclase type V) (Adenylyl cyclase 5) (Ca(2+)-inhibitable adenylyl cyclase ...
It was assumed through most of the last century that cAMP signaling within mammalian cells proceeded mainly, if not exclusively, through activation of PKA (Kuo and Greengard, 1969). More recently, it has been appreciated that at least three major cAMP-dependent signaling pathways exist in rodent and human cells. A large number of molecular biological and pharmacological investigations have been devoted to parsing the relative contributions of PKA, Epac, and now NCS in cAMP-dependent signaling in mammalian, especially neuroendocrine, cells. These investigations have been fraught with the twin difficulties of establishing both (1) that a particular pathway is, in fact, cAMP-dependent and (2) that the pathway, if cAMP-dependent, relies on either canonical (PKA-dependent) or noncanonical (cAMP sensors other than PKA) signaling. Obviously, reagents for selective stimulation or inhibition of the various isoforms of adenylate cyclase have become increasingly central to these efforts. There is a ...
Because it is the only cell in the human body designed to leave the confines of the body, sperm genes echo those of unicellular life forms. An example is the sperm adenylate cyclase that produces cAMP. The sperm adenylate cyclase gene in homology studies bears the most resemblance to the adenylate cyclase found in cyanobacteria. "One way to think about the human genome is that it contains the memory of unicellular life. When the gametes are made, that genetic memory becomes expressed, and genes that are actually most similar to genes found in other unicellular organisms begin to be expressed in the testes," says John Herr at the University of Virginia. "We call this the ancestral gene program that is activated" during sperm production. (Herr has developed two commercial home tests for male infertility, Sperm Check Fertility and Sperm Check Vasectomy, using biomarkers that are unique to the final stage of sperm development in the testes ...
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Since PAM is a potent inhibitor of AC enzyme activity, it was next investigated if the translocation of PAM from the ER to the plasma membrane results in an inhibition of AC activity. Serum-treatment of HeLa cells reduced the intracellular cAMP accumulation (Fig. 19a). Additionally, serum-treatment decreased Gas- and forskolin-stimulated AC activity to 56.7% and 64.7%, respectively, as compared to untreated cells (Fig. 19b). The observed decrease in AC activity was not due to a change in the AC isoform expression or due to an increased AC expression since no changes in the mRNA expression of AC isoforms was detected (Fig. 19c). To determine if the decrease in stimulated AC activity was mediated by PAM, the amount of endogenous PAM was decreased, employing antisense oligonucleotides against PAM as previously described in Scholich et al., 2001. As shown in Fig. 19d, in HeLa cells treated with antisense ODN the amount of PAM, as determined by Western Blot analysis, was decreased as compared to ...
Nine membrane-bound adenylyl cyclase isoforms catalyze the production of the second messenger cyclic AMPs (cAMP) in response to various stimuli. Reduction of adenylyl cyclase activity has well-documented benefits, including for heart disease and pain. These roles have inspired an attempt to develop isoform selective adenylyl cyclase inhibitors. The lack of true selectivity currently limits exploration of functions and/or treatment of dysfunctions involving adenylyl cyclase/cAMP signaling. The present study demonstrated that a panel of inhibitors described as AC5-selective actually does not discriminate between AC5 and AC6. Likewise, the putative AC1-selective inhibitor, NB001 [5-[[2-(6-amino-9H-purin-9-yl)ethyl]amino]-1-pentanol], does not directly target AC1 to reduce cAMP levels. These results lead to a discussion regarding the need to reinterpret literature using AC5/6-selective molecules.. See article at J Pharmacol Exp Ther 2013, 347:265-275.. ...
Background: The two enzyme families involved in the spatiotemporal control of intracellular cAMP are adenylyl cyclases (AC) which account for its synthesis and phosphodiesterases (PDE) which account for its degradation. In adult cardiomyocytes, AC5 and AC6, and PDE3 and PDE4 are the major isoforms of these two enzyme families, respectively. In addition to their role in modulating cardiac contractile function, AC5 and AC6 are differentially regulated in response to different cardiac stress. However the role of each cyclase in cardioprotection is still controversial. Dynamic inter-regulation between ACs and PDEs has never been investigated yet. In this study, we aimed to determine the effect of AC5 and AC6 overexpression on submembrane PDE3 related cAMP hydrolysis in response to β-adrenergic receptor stimulation.. Methods and Results: Mice with cardiac specific overexperssion of AC5 (AC5Tg) and AC6 (AC6Tg) were produced. The spatiotemporal dynamics of cAMP were determined on both AC5Tg and AC6Tg ...
Gene Information This gene encodes a member of the family of adenylate cyclases which are membrane-associated enzymes that catalyze the formation of the secondary messenger cyclic adenosine monophosphate (cAMP). Mouse studies show that adenylate cyclase 4 along with adenylate cyclases 2 and 3 is expressed in olfactory cilia suggesting that several different adenylate cyclases may couple to olfactory receptors and that there may be multiple receptor-mediated mechanisms for the generation of cAMP signals. Alternative splicing results in transcript variants. [provided by RefSeq Nov 2010]. ...
integral component of plasma membrane, adenylate cyclase activity, adenylate cyclase-activating G protein-coupled receptor signaling pathway, axon midline choice point recognition, cAMP biosynthetic process, retinal ganglion cell axon guidance
There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[13]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[13]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...
There are ten isozymes of adenylyl cyclases in mammals, adenylyl cyclase type I-X, (ADCY I-X); In mammals adenylyl cyclase plays an important role in signal transduction pathways in which cAMP is a secondary messenger[12]. ADCY I-IX all share a general structure; They are composed of two trans-membrane regions (M1, M2) which are composed of six membrane-spanning helices and function to keep the enzyme anchored in the membrane, and two cytoplasmic regions (C1, C2) which can be further sub divided (C1a, C1b, C2a, C2b) and are responsible for all catalytic activity, and regulation by G-proteins and forskolin[12]. In solution, the C1a and C2a domains can form heterodimers with each other, either in the same or different enzymes, or they can form homodimers with their identical units on different enzymes[3]. The C1b domain is very large (≈15 kDa) with many regulatory sites, and has a variable structure across isozymes; while the C2b domain is nearly non-existent in many isozymes, and has yet to be ...
Cyclic AMP is an adenine nucleotide containing one phosphate group which is esterified to both the 3- and 5-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. cAMP is synthesized from ATP by adenylate cyclase. Adenylate cyclase is located at the cell membranes. Adenylate cyclase is activated by the hormones glucagon and adrenaline and by G protein. Liver adenylate cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP decomposition into AMP is catalyzed by the enzyme phosphodiesterase ...
To synchronize a network of pacemakers in the Drosophila brain, a neuropeptide receptor specifically associates with adenylate cyclase 3 to create a
A multitude of signalling cascades are implicated in the homeostasis of articular chondrocytes. However, the identity of these signalling pathways is not fully established. The 3, 5-cyclic AMP-mediated signalling system is considered to be a prototype. Adenylyl cyclase (AC) is an effector enzyme responsible for the synthesis of cAMP. There are 10 mammalian AC isoforms and some of these are differentially regulated by calcium/calmodulin (Ca2+/CaM). Ca2+ is known to play an important role in the development and maintenance of skeletal tissues. Ca2+/CaM-dependent AC isoforms and their temporal expression in articular chondrocytes in rats were identified using RT-PCR and immunohistochemistry techniques. All Ca2+/CaM-dependent AC isoforms were expressed in chondrocytes from all age groups examined. Each isoform was differentially expressed in developing and adult articular chondrocytes. Generally, expression of AC isoforms was observed to increase with age, but the increase was not uniform for all Ca2+/CaM
The exoenzyme S regulon is a set of coordinately regulated virulence genes of Pseudomonas aeruginosa. Proteins encoded by the regulon include a type III secretion and translocation apparatus, regulators of gene expression, and effector proteins. The effector proteins include two enzymes with ADP-ribosyltransferase activity (ExoS and ExoT) and an acute cytotoxin (ExoU). In this study, we identified ExoY as a fourth effector protein of the regulon. ExoY is homologous to the extracellular adenylate cyclases of Bordetella pertussis (CyaA) and Bacillus anthracis (EF). The homology among the three adenylate cyclases is limited to two short regions, one of which possesses an ATP-binding motif. In assays for adenylate cyclase activity, recombinant ExoY (rExoY) catalyzed the formation of cAMP with a specific activity similar to the basal activity of CyaA. In contrast to CyaA and EF, rExoY activity was not stimulated or activated by calmodulin. A 500-fold stimulation of activity was detected following the ...
Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.
The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. All nine isoforms share a similar structural organization; thus, AC isoform differences in physiological function are due to different regulatory profiles. A physiological example is Gβγ, which can conditionally enhance stimulation of ACs 2, 4, 5, 6, and 7, but inhibit ACs 1, 3, and 8. There is also pharmacological control of AC isoforms through small molecule inhibitors. Isoform specific AC functions could be explained by regulatory differences as subtle as single amino acid changes. For both pharmacological targeting and known physiological regulators, differences between isoforms are not well understood. Two approaches were taken to explore AC5/6 isoform selectivity. The first approach was to more completely characterize allegedly AC5 selective small molecule AC inhibitors. The other approach was to examine AC isoform
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
These results suggest that differencial regulation of the AC signaling system in various EC types might also be occuring at the G-protein level. 3. Adenylyl Cyclase Isoforms: Recently, a new aspect in the complexity of the AC signaling system has been introduced at the level of adenylyl cyclase. Over the past 5 years, cDNAs encoding eight AC isoforms have been identitied in mammalian cells 77. Since the physiological actions of agonists that bind to AC-stimulating receptors are quite disparate, it is tempting to speculate that some of these receptors might activate different AC isoform(s). 39. Auerbach, R. 1991. Interactions between cancer cells and the endothelium. In Microcirculation in cancer metastasis. W. Orr, M. Buchanan, and L. Weiss, eds. CRC Press, Boca Raton, FL. pp 169-181. 26 40. , L. W. Morrissey, M. Tu, and J. Joseph. 1985. Expression of organ-specific antigens on capillary endothelial cells. Microvasc. Res. 29:401-411. 41. , R. Hallmann, U. Albrecht, and S. Henke-Fahle. 1986. ...
Stimulation by forskolin of the thyroid adenylate cyclase, cyclic AMP accumulation and iodine metabolism.: Forskolin, a diterpene hypotensive drug, activates ad
"Entrez Gene: ADCY2 adenylyl cyclase 2 (brain)". "Adenylate cyclase type 2". UniProt Consortium. Retrieved 28 May 2014. Stengel ... It belongs to the adenylyl cyclase class-3 or guanylyl cyclase family because it contains two guanylate cyclase domains. ADCY2 ... "Adenylate Cyclase 2 (Brain)". Weizmann Institute of Science. Retrieved 28 May 2014. Xu W, Cohen-Woods S, Chen Q, Noor A, Knight ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ...
Haga, T; Ross, EM; Anderson, HJ; Gilman, AG (1977). "Adenylate cyclase permanently uncoupled from hormone receptors in a novel ... Haga, T; Haga, K; Gilman, AG (1977). "Hydrodynamic properties of the beta-adrenergic receptor and adenylate cyclase from wild ... Gilman, AG (1984). "G proteins and dual control of adenylate cyclase". Cell. 36 (3): 577-9. doi:10.1016/0092-8674(84)90336-2. ... Sternweis, PC; Northup, JK; Smigel, MD; Gilman, AG (1981). "The regulatory component of adenylate cyclase. Purification and ...
"Entrez Gene: ADCY3 adenylate cyclase 3". "Gene Cards: ADCY3 Gene". Retrieved 2012-12-30. Human ADCY3 genome location and ADCY3 ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 3 is an enzyme that in humans is encoded by the ADCY3 gene. This gene encodes adenylyl cyclase 3, which ... Haber N, Stengel D, Defer N, Roeckel N, Mattei MG, Hanoune J (Jul 1994). "Chromosomal mapping of human adenylyl cyclase genes ...
1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... Adenylyl cyclase type 6 is an enzyme that in humans is encoded by the ADCY6 gene. This gene encodes adenylyl cyclase 6, which ... 1998). "Molecular diversity of adenylyl cyclases in human and rat myometrium. Correlation with global adenylyl cyclase activity ... ADCY6 adenylate cyclase 6". Human ADCY6 genome location and ADCY6 gene details page in the UCSC Genome Browser. Nakajima D, ...
"Entrez Gene: ADCY9 adenylate cyclase 9". Human ADCY9 genome location and ADCY9 gene details page in the UCSC Genome Browser. ... 1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... Adenylyl cyclase type 9 is an enzyme that in humans is encoded by the ADCY9 gene. Adenylyl cyclase is a membrane bound enzyme ... Cumbay MG, Watts VJ (2004). "Novel regulatory properties of human type 9 adenylate cyclase". J. Pharmacol. Exp. Ther. 310 (1): ...
"Entrez Gene: ADCY7 adenylate cyclase 7". Human ADCY7 genome location and ADCY7 gene details page in the UCSC Genome Browser. ... 1999). "Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 ... The product of this gene is a member of the adenylyl cyclase class-4/guanylyl cyclase enzyme family that is characterized by ... Yan SZ, Tang WJ (2002). "Construction of soluble adenylyl cyclase from human membrane-bound type 7 adenylyl cyclase". Meth. ...
"Entrez Gene: ADCY5 adenylate cyclase 5". Salim S, Sinnarajah S, Kehrl JH, Dessauer CW (May 2003). "Identification of RGS2 and ... Wang SC, Lai HL, Chiu YT, Ou R, Huang CL, Chern Y (2007). "Regulation of type V adenylate cyclase by Ric8a, a guanine ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 5 is an enzyme that in humans is encoded by the ADCY5 gene. ADCY5 has been shown to interact with RGS2. ...
"Entrez Gene: ADCY8 adenylate cyclase 8 (brain)". Human ADCY3 genome location and ADCY3 gene details page in the UCSC Genome ... Barcova M, Speth C, Kacani L, Uberall F, Stoiber H, Dierich MP (Mar 1999). "Involvement of adenylate cyclase and p70(S6)-kinase ... Adenylyl cyclase type 8 is an enzyme that in humans is encoded by the ADCY8 gene. Adenylyl cyclase is a membrane bound enzyme ... Parma J, Stengel D, Gannage MH, Poyard M, Barouki R, Hanoune J (Aug 1991). "Sequence of a human brain adenylyl cyclase partial ...
Brandt DR, Ross EM (January 1985). "GTPase activity of the stimulatory GTP-binding regulatory protein of adenylate cyclase, Gs ... "Purification of the regulatory component of adenylate cyclase". Proceedings of the National Academy of Sciences of the United ... individual subunits of the G protein complex were first identified in 1980 when the regulatory component of adenylate cyclase ... Another example of Gβγ signaling is its effect of activating or inhibiting adenylyl cyclase leading to the intracellular ...
Edema factor is a calmodulin-dependent adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP ( ... The complexation of adenylate cyclase with calmodulin removes calmodulin from stimulating calcium-triggered signaling, thus ...
... diverse biological actions of adenylate cyclase activating polypeptide 1 and is positively coupled to adenylate cyclase. ... Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC1, is a protein that in humans is encoded ... Miampamba M, Germano PM, Arli S, Wong HH, Scott D, Taché Y, Pisegna JR (May 2002). "Expression of pituitary adenylate cyclase- ... Stoffel M, Espinosa R, Trabb JB, Le Beau MM, Bell GI (Oct 1994). "Human type I pituitary adenylate cyclase activating ...
A mnemonic for remembering this subunit is to look at first letter (Gαs = Adenylate Cyclase stimulator). The G protein-coupled ... However, each Gs activates only one adenylate cyclase. Second messenger system Ellis, Claire (Jul 2004). "The state of GPCR ... is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylyl cyclase. It is one of ... The general function of Gs is to activate adenylyl cyclase, which, in turn, produces cAMP, which, in turn activates cAMP- ...
Guanylyl imidodiphosphate is a potent stimulator of adenylate cyclase. It is often used in studies of protein synthesis. ...
Bifunctional hemolysin/adenylate cyclase is a protein that in B. pertussis (the bacteria that causes whooping cough) is encoded ... Carbonetti NH, Artamonova GV, Andreasen C, Bushar N (May 2005). "Pertussis toxin and adenylate cyclase toxin provide a one-two ... This protein in turn is cleaved into a calmodulin-sensitive adenylate cyclase (cyaA-ACD) and hemolysin. Both are virulence ... Ladant D, Ullmann A (April 1999). "Bordatella pertussis adenylate cyclase: a toxin with multiple talents". Trends Microbiol. 7 ...
They always use the activation of adenylate cyclase as the next step in the signal chain. The s stands for stimulation. Their ... Among the target molecules of the active GTPase are adenylate cyclase and ion channels. The heterotrimeric G proteins can be ... The i stands for inhibition of the adenylate cyclase; another effector molecule for this protein family is phospholipase C. ...
The cya gene encodes adenylate cyclase, which produces cAMP. In a cya mutant, the absence of cAMP makes the expression of the ... which influences the activity of adenylate cyclase. (In addition, glucose transport also leads to direct inhibition of the ...
... activates adenylate cyclase in the absence of ligand. GPR3 is expressed in mammalian oocytes where it maintains meiotic ... 1995). "Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase". Biochem. J ... "Molecular cloning of an orphan G-protein-coupled receptor that constitutively activates adenylate cyclase". Biochem. J. 309 ( ...
Zhang ZH, Wu SD, Gao H, Shi G, Jin JZ, Kong J, Tian Z, Su Y (March 2006). "Expression of pituitary adenylate cyclase-activating ... Wei Y, Mojsov S (1997). "Tissue specific expression of different human receptor types for pituitary adenylate cyclase ... VIPR2 transduction results in upregulation of adenylate cyclase activity. Furthermore, VIPR2 mediates the anti-inflammatory ... Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are homologous peptides that ...
link) May, DC; Ross, EM; Gilman, AG; Smigel, MD (1985). "Reconstitution of catecholamine-stimulated adenylate cyclase activity ... 1984). "Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine ... activates hormone-sensitive adenylate cyclase. Gα subunits consist of two domains, the GTPase domain, and the alpha-helical ...
One of the most important of the regulated toxins is adenylate cyclase toxin, which aids in the evasion of innate immunity. The ... Fiser R, Masín J, Basler M, Krusek J, Spuláková V, Konopásek I, Sebo P (2007). "Third activity of Bordetella adenylate cyclase ... Gray MC, Donato GM, Jones FR, Kim T, Hewlett EL (2004). "Newly secreted adenylate cyclase toxin is responsible for intoxication ... Hewlett EL, Donato GM, Gray MC (2006). "Macrophage cytotoxicity produced by adenylate cyclase toxin from Bordetella pertussis: ...
Adenylate cyclase is inhibited by agonists of adenylate cyclase inhibitory G (Gi)-protein-coupled receptors. Liver adenylate ... Adenylate cyclase is activated by a range of signaling molecules through the activation of adenylate cyclase stimulatory G (Gs ... This occurs through inhibition of the cAMP-producing enzyme, adenylate cyclase, as a side-effect of glucose transport into the ... cyclase responds more strongly to glucagon, and muscle adenylate cyclase responds more strongly to adrenaline. cAMP ...
"Adenylate-cyclase VI transforms ventricular cardiomyocytes into biological pacemaker cells". Tissue Engineering Part A. 16 (6 ... "Adenylate Cyclase" gene into the heart muscle a biological cardiac pacemaker can be created. More recently a gene called TBX18 ...
"Entrez Gene: CAP1 CAP, adenylate cyclase-associated protein 1 (yeast)". Hubberstey, A; Yu G; Loewith R; Lakusta C; Young D (Jun ... Adenylyl cyclase-associated protein 1 is an enzyme that in humans is encoded by the CAP1 gene. The protein encoded by this gene ... Yu G, Swiston J, Young D (1994). "Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins ... 2004). "Crystal structure of the actin binding domain of the cyclase-associated protein". Biochemistry. 43 (33): 10628-41. doi: ...
... a process regulator related to adenylate cyclase proteins; a profilin with a molecular weight of approximately 14 kDa that is ...
H2 receptors are positively coupled to adenylate cyclase via Gs. It is a potent stimulant of cAMP production, which leads to ...
... influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase ...
Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle. Download Prime PubMed ... Pituitary Adenylate Cyclase-activating Peptide as a Neurotransmitter in the Canine Ileal Circular Muscle. J Pharmacol Exp Ther. ... Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle. J Pharmacol Exp Ther ... "Pituitary Adenylate Cyclase-activating Peptide as a Neurotransmitter in the Canine Ileal Circular Muscle." The Journal of ...
Article Pituitary adenylate cyclase-activating polypeptide 38-mediated rin activation requires src and contributes to the ... Pituitary adenylate cyclase-activating polypeptide 38-mediated .... Pituitary adenylate cyclase-activating polypeptide 38- ... No comments were found for Pituitary adenylate cyclase-activating polypeptide 38-mediated rin activation requires src and ... Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neuropeptide that acts through G-protein-coupled ...
Neurotrophic and neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on mesencephalic ...
Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration ... Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration ... Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration ... Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective function in dopamine-based neurodegeneration ...
Downs, R. W., Sekura, R. D., Levine, M. A., & Spiegel, A. M. (1985). The inhibitory adenylate cyclase coupling protein in ... The inhibitory adenylate cyclase coupling protein in pseudohypoparathyroidism. Robert W. Downs, Ronald D. Sekura, Michael A. ... The inhibitory adenylate cyclase coupling protein in pseudohypoparathyroidism. / Downs, Robert W.; Sekura, Ronald D.; Levine, ... The inhibitory adenylate cyclase coupling protein in pseudohypoparathyroidism. Journal of Clinical Endocrinology and Metabolism ...
Pituitary Adenylate Cyclase-Activating Polypeptide*Pituitary Adenylate Cyclase-Activating Polypeptide. *Pituitary Adenylate ... Pituitary Adenylate Cyclase Activating Polypeptide 38*Pituitary Adenylate Cyclase Activating Polypeptide 38 ... Pituitary Adenylate Cyclase Activating Polypeptide 27*Pituitary Adenylate Cyclase Activating Polypeptide 27 ... "Pituitary Adenylate Cyclase-Activating Polypeptide" by people in this website by year, and whether "Pituitary Adenylate Cyclase ...
Pituitary Adenylate Cyclase Activating Polypeptide , Pituitary Adenylate Cyclase Activating Polypeptide 27 , Pituitary ... Pituitary Adenylate Cyclase-Activating Polypeptide 2.. Chemicals ← Biological Factors ← Intercellular Signaling Peptides and ... Pituitary Adenylate Cyclase-Activating Polypeptide Equivalent Terms PACAP , PACAP27 , PACAP-27 , PACAP38 , PACAP-38 , ... Adenylate Cyclase Activating Polypeptide 38 Definition A multi-function neuropeptide that acts throughout the body by elevating ...
Bordetella pertussis adenylate cyclase. Penetration into host cells.: Exposure of Chinese hamster ovary, mouse adrenal cortex ... In Y-1 adrenal cells the urea-extract adenylate cyclase stimulates steroidogenesis. Anti-(B. pertussis) antibodies inhibit ... THP-1 and U-937 cells and human erythrocytes to adenylate-cyclase-containing urea extracts of Bordetella pertussis (strain 114 ... have no inhibitory effect on the accumulation of intracellular cAMP promoted by the internalized adenylate cyclase of urea ...
Pituitary adenylate cyclase-activating polypeptide (PACAP) plays several important roles in vasodilation, neurotransmission, ... Pituitary adenylate cyclase-activating polypeptide expression in peripheral blood mononuclear cells of migraineurs. *Lei Hou1. ... Hou, L., Wan, D., Dong, Z. et al. Pituitary adenylate cyclase-activating polypeptide expression in peripheral blood mononuclear ... Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal peptide (VIP)/secretin/ ...
The adenylate cyclase toxin (AC toxin) is necessary for disease caused by Bordetella pertussis, which has reemerged in the ... Bordetella adenylate cyclase toxin: the role of cell interaction in toxin functio Eby, Joshua Clark University of Virginia, ... Bordetella adenylate cyclase toxin: the role of cell interaction in toxin functio. Eby, Joshua Clark / University of Virginia. ... Bordetella adenylate cyclase toxin: the role of cell interaction in toxin functio. Eby, Joshua Clark / University of Virginia. ...
Ca2 Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin ACT Endocytosis. Cell Physiology and Expression of ... Ca2 Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin ACT Endocytosis. Cell Physiology and Expression of ... Ca2 Influx and Tyrosine Kinases Trigger Bordetella Adenylate Cyclase Toxin ACT Endocytosis. Cell Physiology and Expression of ... This pathogenic bacterium produces a unique adenylate cyclase toxin ACT which enters human phagocytes and catalyzes the ...
N2 - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and ... AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and ... Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and ... abstract = "Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland ...
Sekiya K, Nagasaki H, Ozaki N, Suzuki A, Miura Y, Oiso Y. Pituitary adenylate cyclase-activating polypeptide prevents cytokine- ... Sekiya, K., Nagasaki, H., Ozaki, N., Suzuki, A., Miura, Y., & Oiso, Y. (2000). Pituitary adenylate cyclase-activating ... Sekiya, K, Nagasaki, H, Ozaki, N, Suzuki, A, Miura, Y & Oiso, Y 2000, Pituitary adenylate cyclase-activating polypeptide ... Pituitary adenylate cyclase-activating polypeptide prevents cytokine-induced cytotoxicity via inhibition of inducible nitric ...
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide. Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, ... Pituitary Adenylate Cyclase-Activating Polypeptide; 0 / Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; ...
... replaced ATP as the substrate for adenylate cyclase, implying that adenylate cyclase was inactivated by phosphorylation caused ... In a standard assay system using rat adipocyte plasma membrane as the source of adenylate cyclase, the FR inhibited adenylate ... The mechanism of action of FR on inhibition of adenylate cyclase appears to be related to the phosphorylation of certain ... Action of feedback regulator on adenylate cyclase. R J Ho and E W Sutherland ...
Extracellular adenylate cyclase is an adenylate cyclase produced by Bordetella pertussis. Kessin RH, Franke J (April 1986). " ... Ladant D, Brezin C, Alonso JM, Crenon I, Guiso N (December 1986). "Bordetella pertussis adenylate cyclase. Purification, ... "Secreted adenylate cyclase of Bordetella pertussis: calmodulin requirements and partial purification of two forms". J. ...
Guanylate_cyc; Adenylate and Guanylate cyclase catalytic domain. pfam16214. Location:259 → 376. AC_N; Adenylyl cyclase N- ... adenylate cyclase 9. See related. Ensembl:ENSCVAG00000003552 Gene type. protein coding. RefSeq status. MODEL. Organism. ... adcy9 adenylate cyclase 9 [ Cyprinodon variegatus (sheepshead minnow) ] Gene ID: 107095220, updated on 13-Oct-2018 ... XM_015391219.1 → XP_015246705.1 adenylate cyclase type 9. Related. ENSCVAP00000021468.1, ENSCVAT00000011721.1. Conserved ...
Treatment of the adenylate cyclase with cholera toxin caused a decrease of 96% in the rate constant of the turn-off reaction. ... The regulatory GTPase cycle of turkey erythrocyte adenylate cyclase.. Cassel D, Levkovitz H, Selinger Z. ... It has recently been suggested that adenylate cyclase activity is controlled by a regulatory cycle consisting of two reactions ... a hormone induced formation of the active adenylate cyclase-GTP complex, and a subsequent turn-off reaction in which hydrolysis ...
Pituitary adenylate cyclase-activating peptide has been shown to interact with secretin receptor. Adenylate cyclase Pituitary ... This gene encodes adenylate cyclase-activating polypeptide 1. Mediated by adenylate cyclase-activating polypeptide 1 receptors ... this polypeptide stimulates adenylate cyclase and subsequently increases the cAMP level in target cells. Adenylate cyclase- ... Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ADCYAP1 ...
We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior ... Salomon Y, Londos C, Rodbell M (1974) A highly sensitive adenylate cyclase assay. Anal Biochem 58:541-548Google Scholar ... We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior ... Harden TK (1983) Agonist-induced desensitization of the β-adrenergic receptor-linked to adenylate cyclase. Pharmacol Rev 35:5- ...
In: Pituitary Adenylate Cyclase Activating Polypeptide-PACAP. Springer, Cham, pp 757-766CrossRefGoogle Scholar ... Lezak KR, Roelke E, Harris OM, Choi I, Edwards S, Gick N et al (2014) Pituitary adenylate cyclase-activating polypeptide (PACAP ... Miles OW, Thrailkill EA, Linden AK, May V, Bouton ME, Hammack SE (2017) Pituitary adenylate cyclase-activating peptide in the ... May V, Lutz E, MacKenzie C, Schutz KC, Dozark K, Braas KM (2010) Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC ...
IPR000274. Adenylate_cyclase_1. IPR024686. Adenylate_cyclase_1_CS. IPR024685. Adenylate_cyclase_1_N. ... IPR000274. Adenylate_cyclase_1. IPR024686. Adenylate_cyclase_1_CS. IPR024685. Adenylate_cyclase_1_N. ... PS01092. ADENYLATE_CYCLASE_1_1. 1 hit. PS01093. ADENYLATE_CYCLASE_1_2. 1 hit. ... PS01092. ADENYLATE_CYCLASE_1_1. 1 hit. PS01093. ADENYLATE_CYCLASE_1_2. 1 hit. ...
Adenylate cyclase of Escherichia coli K12 has been purified 17,000-fold to near homogeneity from a 5-fold overproducing strain ... Purification and characterization of adenylate cyclase from Escherichia coli K12.. Yang J.K., Epstein W. ...
Browse our Adenylate Cyclase 1 Antibody catalog backed by our Guarantee+. ... Adenylate Cyclase 1 Antibodies available through Novus Biologicals. ...
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  • This suggests that a portion of the cyclase is associated with cells in a form not accessible to antibody or washing but accessible to substrate, which we interpret as internalized enzyme with a short lifetime. (mysciencework.com)
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