Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity.

Stress wherein emotional factors predominate.

A behavior therapy technique in which deep muscle relaxation is used to inhibit the effects of graded anxiety-evoking stimuli.

Coordinate set of non-specific behavioral responses to non-psychiatric illness. These may include loss of APPETITE or LIBIDO; disinterest in ACTIVITIES OF DAILY LIVING; or withdrawal from social interaction.

A class of traumatic stress disorders that is characterized by the significant dissociative states seen immediately after overwhelming trauma. By definition it cannot last longer than 1 month, if it persists, a diagnosis of post-traumatic stress disorder (STRESS DISORDERS, POST-TRAUMATIC) is more appropriate.

Historical term for a chronic, but fluctuating, disorder beginning in early life and characterized by recurrent and multiple somatic complaints not apparently due to physical illness. This diagnosis is not used in contemporary practice.

Standardized tests designed to measure abilities, as in intelligence, aptitude, and achievement tests, or to evaluate personality traits.

Subjective feeling of having committed an error, offense or sin; unpleasant feeling of self-criticism. These result from acts, impulses, or thoughts contrary to one's personal conscience.

Feeling or emotion of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.

Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.

A group of disorders characterized by physical symptoms that are affected by emotional factors and involve a single organ system, usually under AUTONOMIC NERVOUS SYSTEM control. (American Psychiatric Glossary, 1988)

G-protein-coupled receptor kinases that mediate agonist-dependent PHOSPHORYLATION and desensitization of BETA-ADRENERGIC RECEPTORS.

A state of harmony between internal needs and external demands and the processes used in achieving this condition. (From APA Thesaurus of Psychological Index Terms, 8th ed)

Depressive states usually of moderate intensity in contrast with major depression present in neurotic and psychotic disorders.

Heterocyclic compounds of a ring with SULFUR and two NITROGEN atoms fused to a BENZENE ring. Members inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.

Instructional materials used in teaching.

A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response.

Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin.

An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.

An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.

Behavior-response patterns that characterize the individual.

A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS. It may play an essential role in regulating myocardial contractile response.

Part of the body in humans and primates where the arms connect to the trunk. The shoulder has five joints; ACROMIOCLAVICULAR joint, CORACOCLAVICULAR joint, GLENOHUMERAL joint, scapulathoracic joint, and STERNOCLAVICULAR joint.

The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves.

Systematic and thorough inspection of the patient for physical signs of disease or abnormality.

Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.

A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.

Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.

An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.

A family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. They are regulatory proteins that play a role in G-protein-coupled receptor densensitization.

A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.

Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.

Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.

Those affective states which can be experienced and have arousing and motivational properties.

Elements of limited time intervals, contributing to particular results or situations.

Professionals qualified by graduation from an accredited school of nursing and by passage of a national licensing examination to practice nursing. They provide services to patients requiring assistance in recovering or maintaining their physical or mental health.

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.

Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.

The rate dynamics in chemical or physical systems.

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.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A G-protein-coupled receptor kinase subtype that is primarily expressed in the MYOCARDIUM and may play a role in the regulation of cardiac functions.

A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.

Assessment of psychological variables by the application of mathematical procedures.

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.

Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.

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.

An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.

Tumors or cancer of the human BREAST.

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.

Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.

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.-.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.

A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.

Established cell cultures that have the potential to propagate indefinitely.

A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).

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.

An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.

Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.

Immunologically mediated adverse reactions to medicinal substances used legally or illegally.

A class of traumatic stress disorders with symptoms that last more than one month. There are various forms of post-traumatic stress disorder, depending on the time of onset and the duration of these stress symptoms. In the acute form, the duration of the symptoms is between 1 to 3 months. In the chronic form, symptoms last more than 3 months. With delayed onset, symptoms develop more than 6 months after the traumatic event.

A technique that induces the processing of disturbing memories and experiences, by stimulating neural mechanisms that are similar to those activated during REM sleep. The technique consists of eye movements following side-to-side movements of the index and middle fingers, or the alternate tapping of the hands on the knees. This procedure triggers the processing of information, thus facilitating the connection of neural networks.

The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).

Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.

Public attitudes toward health, disease, and the medical care system.

New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.

Standardized procedures utilizing rating scales or interview schedules carried out by health personnel for evaluating the degree of mental illness.

The term "United States" in a medical context often refers to the country where a patient or study participant resides, and is not a medical term per se, but relevant for epidemiological studies, healthcare policies, and understanding differences in disease prevalence, treatment patterns, and health outcomes across various geographic locations.

Rapidly decreasing response to a drug or physiologically active agent after administration of a few doses. In immunology, it is the rapid immunization against the effect of toxic doses of an extract or serum by previous injection of small doses. (Dorland, 28th ed)

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.

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.

The opening and closing of ion channels due to a stimulus. The stimulus can be a change in membrane potential (voltage-gated), drugs or chemical transmitters (ligand-gated), or a mechanical deformation. Gating is thought to involve conformational changes of the ion channel which alters selective permeability.

A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.

An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.

The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.

The teaching or training of patients concerning their own health needs.

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.

A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.

A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.

The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.

The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival.

A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension, and NEUROPATHIC PAIN. The receptor comprises three P2X3 subunits. The P2X3 subunits are also associated with P2X2 RECEPTOR subunits in a heterotrimeric receptor variant.

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.

The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.

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.

Bluish-colored region in the superior angle of the FOURTH VENTRICLE floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the PERIAQUEDUCTAL GRAY.

The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.

A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals.

Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.

An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.

A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.

Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.

Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for Social Security and workmen's compensation benefits.

Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.

Social and economic factors that characterize the individual or group within the social structure.

Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.

Drugs that selectively bind to and activate beta-adrenergic receptors.

A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.

An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.

The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures.

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.

Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.

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.

A purinergic P2X neurotransmitter receptor involved in sensory signaling of TASTE PERCEPTION, chemoreception, visceral distension and NEUROPATHIC PAIN. The receptor comprises three P2X2 subunits. The P2X2 subunits also have been found associated with P2X3 RECEPTOR subunits in a heterotrimeric receptor variant.

Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.

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.

The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.

One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.

In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.

Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.

A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.

The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.

Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.

A class of histamine receptors discriminated by their pharmacology and mode of action. Most histamine H1 receptors operate through the inositol phosphate/diacylglycerol second messenger system. Among the many responses mediated by these receptors are smooth muscle contraction, increased vascular permeability, hormone release, and cerebral glyconeogenesis. (From Biochem Soc Trans 1992 Feb;20(1):122-5)

Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.

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.

A highly selective and specific beta antagonist that is used to characterize beta-adrenoceptors.

A family of proton-gated sodium channels that are primarily expressed in neuronal tissue. They are AMILORIDE-sensitive and are implicated in the signaling of a variety of neurological stimuli, most notably that of pain in response to acidic conditions.

Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.

Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.

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'-(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.

A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.

Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.

Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).

A subclass of serotonin receptors that form cation channels and mediate signal transduction by depolarizing the cell membrane. The cation channels are formed from 5 receptor subunits. When stimulated the receptors allow the selective passage of SODIUM; POTASSIUM; and CALCIUM.

Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).

Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)

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 surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.

The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.

An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.

The most common inhibitory neurotransmitter in the central nervous system.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.

A potent vasodilator agent that increases peripheral blood flow.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

A source of inorganic fluoride which is used topically to prevent dental caries.

An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.

A family of inwardly-rectifying potassium channels that are activated by PERTUSSIS TOXIN sensitive G-PROTEIN-COUPLED RECEPTORS. GIRK potassium channels are primarily activated by the complex of GTP-BINDING PROTEIN BETA SUBUNITS and GTP-BINDING PROTEIN GAMMA SUBUNITS.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.

A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.

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).

A narcotic analgesic morphinan used as a sedative in veterinary practice.

The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.

Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.

A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.

Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.

An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.

A G-protein-coupled receptor kinase subtype that is primarily expressed in the TESTES and BRAIN. Variants of this subtype exist due to multiple alternative splicing of its mRNA.

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.

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.

A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)

Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.

Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.

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.

A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.

Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.

Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.

A subclass of purinergic P2 receptors that signal by means of a ligand-gated ion channel. They are comprised of three P2X subunits which can be identical (homotrimeric form) or dissimilar (heterotrimeric form).

A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.

The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.

A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.

Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.

A purinergic P2X neurotransmitter receptor found at sympathetically innervated SMOOTH MUSCLE. It may play a functional role regulating the juxtoglomerular apparatus of the KIDNEY.

A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.

A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.

A subclass of muscarinic receptor that mediates cholinergic-induced contraction in a variety of SMOOTH MUSCLES.

Venoms produced by frogs, toads, salamanders, etc. The venom glands are usually on the skin of the back and contain cardiotoxic glycosides, cholinolytics, and a number of other bioactive materials, many of which have been characterized. The venoms have been used as arrow poisons and include bufogenin, bufotoxin, bufagin, bufotalin, histrionicotoxins, and pumiliotoxin.

A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to GI-GO G-PROTEINS resulting in decreased intracellular CYCLIC AMP levels.

The ability of a substrate to allow the passage of ELECTRONS.

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.

Drugs that bind to and activate excitatory amino acid receptors.

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.

A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.

Proteins prepared by recombinant DNA technology.

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.

A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.

Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety.

An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.

A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).

An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawal.

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.

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.

A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.

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.

A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.

A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.

A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.

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.

Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin.

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.

An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)

One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.

Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.

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.

Maleimides are a class of chemically reactive compounds containing a maleimide functional group, which can undergo addition reactions with nucleophiles such as thiols, making them useful for the formation of covalent bonds in various bioconjugation and material synthesis applications.