Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from PREKALLIKREIN by FACTOR XIIA. It activates FACTOR XII; FACTOR VII; and PLASMINOGEN. It is selective for both ARGININE and to a lesser extent LYSINE bonds. EC 3.4.21.34.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77).Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Receptor, Bradykinin B1: A subtype of BRADYKININ RECEPTOR that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.Kinins: A generic term used to describe a group of polypeptides with related chemical structures and pharmacological properties that are widely distributed in nature. These peptides are AUTACOIDS that act locally to produce pain, vasodilatation, increased vascular permeability, and the synthesis of prostaglandins. Thus, they comprise a subset of the large number of mediators that contribute to the inflammatory response. (From Goodman and Gilman's The Pharmacologic Basis of Therapeutics, 8th ed, p588)Kallidin: A decapeptide bradykinin homolog cleaved from kininogen by kallikreins. It is a smooth-muscle stimulant and hypotensive agent that acts by vasodilatation.Kininogens: Endogenous peptides present in most body fluids. Certain enzymes convert them to active KININS which are involved in inflammation, blood clotting, complement reactions, etc. Kininogens belong to the cystatin superfamily. They are cysteine proteinase inhibitors. HIGH-MOLECULAR-WEIGHT KININOGEN; (HMWK); is split by plasma kallikrein to produce BRADYKININ. LOW-MOLECULAR-WEIGHT KININOGEN; (LMWK); is split by tissue kallikrein to produce KALLIDIN.Factor XIIa: Activated form of factor XII. In the initial event in the intrinsic pathway of blood coagulation, kallikrein (with cofactor HIGH MOLECULAR WEIGHT KININOGEN) cleaves factor XII to XIIa. Factor XIIa is then further cleaved by kallikrein, plasmin, and trypsin to yield smaller factor XII fragments (Hageman-Factor fragments). These fragments increase the activity of prekallikrein to kallikrein but decrease the procoagulant activity of factor XII.Factor XII: Stable blood coagulation factor activated by contact with the subendothelial surface of an injured vessel. Along with prekallikrein, it serves as the contact factor that initiates the intrinsic pathway of blood coagulation. Kallikrein activates factor XII to XIIa. Deficiency of factor XII, also called the Hageman trait, leads to increased incidence of thromboembolic disease. Mutations in the gene for factor XII that appear to increase factor XII amidolytic activity are associated with HEREDITARY ANGIOEDEMA TYPE III.Kallikrein-Kinin System: A system of metabolic interactions by products produced in the distal nephron of the KIDNEY. These products include KALLIKREIN; KININS; KININASE I; KININASE II; and ENKEPHALINASE. This system participates in the control of renal functions. It interacts with the RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM to regulate BLOOD PRESSURE, generation of PROSTAGLANDINS, release of VASOPRESSINS, and WATER-ELECTROLYTE BALANCE.Tissue Kallikreins: A family of trypsin-like SERINE ENDOPEPTIDASES that are expressed in a variety of cell types including human prostate epithelial cells. They are formed from tissue prokallikrein by action with TRYPSIN. They are highly similar to PROSTATE-SPECIFIC ANTIGEN.Prekallikrein: A plasma protein which is the precursor of kallikrein. Plasma that is deficient in prekallikrein has been found to be abnormal in thromboplastin formation, kinin generation, evolution of a permeability globulin, and plasmin formation. The absence of prekallikrein in plasma leads to Fletcher factor deficiency, a congenital disease.Receptors, Neurotransmitter: 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.Kaolin: The most common mineral of a group of hydrated aluminum silicates, approximately H2Al2Si2O8-H2O. It is prepared for pharmaceutical and medicinal purposes by levigating with water to remove sand, etc. (From Merck Index, 11th ed) The name is derived from Kao-ling (Chinese: "high ridge"), the original site. (From Grant & Hackh's Chemical Dictionary, 5th ed)Complement C1 Inactivator Proteins: Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.Kininogen, High-Molecular-Weight: A plasma protein, molecular weight of 110 kD, that normally exists in plasma in a 1:1 complex with PREKALLIKREIN. HMWK is split by plasma kallikrein to produce BRADYKININ. The complex is a cofactor in the activation of coagulation factor XII. The product of this reaction, XIIa, in turn activates prekallikrein to KALLIKREINS. (From Stedman, 26th ed)Kininogen, Low-Molecular-Weight: A protein, molecular weight 50 kD, located in various normal tissues. Upon cleavage by KALLIKREINS, it forms KALLIDIN. Kallidin, in turn, is converted into BRADYKININ. (From Stedman, 25th ed)Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.Aprotinin: A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)Angioedema: Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.Factor XI: Stable blood coagulation factor involved in the intrinsic pathway. The activated form XIa activates factor IX to IXa. Deficiency of factor XI is often called hemophilia C.Lysine Carboxypeptidase: A metallocarboxypeptidase that removes C-terminal basic amino acid from peptides and proteins, with preference shown for lysine over arginine. It is a plasma zinc enzyme that inactivates bradykinin and anaphylatoxins.Inosine Triphosphate: Inosine 5'-(tetrahydrogen triphosphate). An inosine nucleotide containing three phosphate groups esterified to the sugar moiety. Synonym: IRPPP.Plasma: The residual portion of BLOOD that is left after removal of BLOOD CELLS by CENTRIFUGATION without prior BLOOD COAGULATION.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Factor XIa: Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium.Fibrinolysin: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.Complement C1 Inhibitor Protein: An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.Complement C1s: A 77-kDa subcomponent of complement C1, encoded by gene C1S, is a SERINE PROTEASE existing as a proenzyme (homodimer) in the intact complement C1 complex. Upon the binding of COMPLEMENT C1Q to antibodies, the activated COMPLEMENT C1R cleaves C1s into two chains, A (heavy) and B (light, the serine protease), linked by disulfide bonds yielding the active C1s. The activated C1s, in turn, cleaves COMPLEMENT C2 and COMPLEMENT C4 to form C4b2a (CLASSICAL C3 CONVERTASE).Macroglobulins: Serum globulins with high molecular weight. (Dorland, 28th ed)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.Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.Peptidyl-Dipeptidase A: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.Inositol Phosphates: Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.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.Kinetics: The rate dynamics in chemical or physical systems.EsterasesCaptopril: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.Benzoylarginine Nitroanilide: A chromogenic substrate that permits direct measurement of peptide hydrolase activity, e.g., papain and trypsin, by colorimetry. The substrate liberates p-nitroaniline as a chromogenic product.Factor XII Deficiency: An absence or reduced level of blood coagulation factor XII. It normally occurs in the absence of patient or family history of hemorrhagic disorders and is marked by prolonged clotting time.Phosphatidylinositols: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Angioedemas, Hereditary: Inherited disorders that are characterized by subcutaneous and submucosal EDEMA in the upper RESPIRATORY TRACT and GASTROINTESTINAL TRACT.Blood Coagulation: The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot.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.Chromogenic Compounds: Colorless, endogenous or exogenous pigment precursors that may be transformed by biological mechanisms into colored compounds; used in biochemical assays and in diagnosis as indicators, especially in the form of enzyme substrates. Synonym: chromogens (not to be confused with pigment-synthesizing bacteria also called chromogens).Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Trypsin Inhibitor, Kunitz Soybean: A high-molecular-weight protein (approximately 22,500) containing 198 amino acid residues. It is a strong inhibitor of trypsin and human plasmin.Complement C1: The first complement component to act in the activation of CLASSICAL COMPLEMENT PATHWAY. It is a calcium-dependent trimolecular complex made up of three subcomponents: COMPLEMENT C1Q; COMPLEMENT C1R; and COMPLEMENT C1S at 1:2:2 ratios. When the intact C1 binds to at least two antibodies (involving C1q), C1r and C1s are sequentially activated, leading to subsequent steps in the cascade of COMPLEMENT ACTIVATION.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.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.Complement Activating Enzymes: Enzymes that activate one or more COMPLEMENT PROTEINS in the complement system leading to the formation of the COMPLEMENT MEMBRANE ATTACK COMPLEX, an important response in host defense. They are enzymes in the various COMPLEMENT ACTIVATION pathways.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Fibrinolysis: The natural enzymatic dissolution of FIBRIN.Blood Coagulation Tests: Laboratory tests for evaluating the individual's clotting mechanism.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.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.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.Muscle, Smooth: 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)Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Submandibular Gland: One of two salivary glands in the neck, located in the space bound by the two bellies of the digastric muscle and the angle of the mandible. It discharges through the submandibular duct. The secretory units are predominantly serous although a few mucous alveoli, some with serous demilunes, occur. (Stedman, 25th ed)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.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Inositol 1,4,5-Trisphosphate: 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.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Oligopeptides: Peptides composed of between two and twelve amino acids.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process.TritiumBinding, 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.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36.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.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.-.Arginine: An essential amino acid that is physiologically active in the L-form.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Plasma Cells: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20)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.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Thrombin: An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.Signal 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.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.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Plasminogen: Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.Urokinase-Type Plasminogen Activator: A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.Chromatography: Techniques used to separate mixtures of substances based on differences in the relative affinities of the substances for mobile and stationary phases. A mobile phase (fluid or gas) passes through a column containing a stationary phase of porous solid or liquid coated on a solid support. Usage is both analytical for small amounts and preparative for bulk amounts.Tosylarginine Methyl Ester: Arginine derivative which is a substrate for many proteolytic enzymes. As a substrate for the esterase from the first component of complement, it inhibits the action of C(l) on C(4).Transfection: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
  • 1 The classic human tissue kallikrein KLK1 (hK1), notably present in renal tissue and released into urine, has been used as a pharmacological agent in animals, lately under the form of DNA expression vectors used in gene therapy strategies or transgenic animals. (ahajournals.org)
  • Experimental studies revealed that mice lacking the B2 receptor gene were more likely to develop hypertension, cardiac hypertrophy, and myocardial damage. (hmdb.ca)
  • For example, bradykinin synthesis and B 2 -receptor gene expression are activated in the developing rat kidney ( 7 , 8 ). (physiology.org)
  • Furthermore, it was shown that mice deficient in the B 2 -receptor gene and salt loaded during embryogenesis acquired an aberrant kidney phenotype incompatible with postnatal survival ( 9 ). (physiology.org)
  • In this study, we evaluated the effects of adenovirus-mediated human tissue kallikrein gene (Ad.CMV-cHK) delivery in a mouse model of arterial remodeling induced by permanent alteration in shear stress conditions. (ahajournals.org)
  • Expression of human tissue kallikrein (HK) mRNA was detected in mouse carotid artery, aorta, kidney, heart, and liver, and recombinant HK was present in the urine and plasma of mice receiving HK gene. (ahajournals.org)
  • Kallikrein gene transfer resulted in increases in urinary kinin, cGMP, and cAMP levels. (ahajournals.org)
  • 0.05) in mice with knockout of the kinin B 2 receptor gene compared with wild-type control mice (J129Sv mice). (ahajournals.org)
  • These results provide new insight into the role of the tissue kallikrein-kinin system in vascular remodeling and suggest the application of HK gene therapy to treat restenosis and atherosclerosis. (ahajournals.org)
  • 12 13 14 15 Recently, adenovirus-mediated human tissue kallikrein (HK) gene delivery proved to be an efficient strategy to increase local or circulating kinin levels for a limited period of time. (ahajournals.org)
  • We investigated the role of the kallikrein-kinin system in cardiac function and glucose utilization in the streptozotocin (STZ)-induced diabetic rat model using a gene transfer approach. (diabetesjournals.org)
  • Adenovirus harboring the human tissue kallikrein gene was administered to rats by intravenous injection at 1 week after STZ treatment. (diabetesjournals.org)
  • Human kallikrein transgene expression was detected in the serum and urine of STZ-induced diabetic rats after gene transfer. (diabetesjournals.org)
  • Kallikrein gene delivery significantly reduced blood glucose levels and cardiac glycogen accumulation in STZ-induced diabetic rats. (diabetesjournals.org)
  • Kallikrein gene transfer also significantly attenuated elevated plasma triglyceride and cholesterol levels, food and water intake, and loss of body weight gain, epididymal fat pad, and gastrocnemius muscle weight in STZ-induced diabetic rats. (diabetesjournals.org)
  • Cardiac function was significantly improved after kallikrein gene transfer as evidenced by increased cardiac output and ±Δ P /Δ t (maximum speed of contraction/relaxation), along with elevated cardiac sarco(endo)plasmic reticulum (Ca 2+ + Mg 2+ )-ATPase (SERCA)-2a, phosphorylated phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes of cardiac and skeletal muscle. (diabetesjournals.org)
  • Kallikrein gene delivery also increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation, resulting in decreased GSK-3β activity in the heart. (diabetesjournals.org)
  • We showed that kallikrein gene transfer improves myocardial contractility, reduced glycogen accumulation, and hyperlipidemia through increased phospholamban phosphorylation and sarco(endo)plasmic reticulum (Ca 2+ + Mg 2+ )-ATPase (SERCA)-2a levels, GLUT4 translocation, and activation of the Akt-glycogen synthase kinase (GSK) signaling pathway in STZ-induced diabetic rats. (diabetesjournals.org)
  • It has recently been reported that disruption of the bradykinin B 2 receptor gene in mice (B 2 −/− mice) increased BP, heart weight, and LV chamber dimension. (ahajournals.org)
  • Intracellular receptors that are involved in the regulation of specific gene transcription have been identified in neuroendocrine structures, and they account for the many molecular events that are involved in steroid hormone action. (pnas.org)
  • The gene of the bradykinin does not exist: it is the product of a post-transcriptional edit and post-translational modifications performed by various enzymes. (diff.org)
  • Case 1 seems to be histamine-mediated and Case 2 bradykinin-mediated based on the history and examination. (emdocs.net)
  • Histamine acts through four classes of receptors, designated H 1 through H 4 . (mhmedical.com)
  • 4 Thus, the lack of inhibition by C1-INH leads to unregulated synthesis of bradykinin and complement fragments. (uspharmacist.com)
  • Kinins stimulate the release of nitric oxide (NO) and prostacyclin (PGI 2 ) through the activation of bradykinin (BK) B 2 receptors expressed by VECs. (ahajournals.org)
  • Intact kinin binds to the bradykinin B2 receptor and transduces signals through nitric oxide (NO)-cGMP and prostacyclin-cAMP pathways, thereby modulating a broad spectrum of cellular functions ( 2 ). (diabetesjournals.org)
  • We postulate that bradykinin plays a protective role in cardiac anaphylaxis by accumulating at the luminal surface of the coronary endothelium and promoting, in an autocrine mode, a B 2 -receptor-mediated production of nitric oxide and prostacyclin in concentrations sufficient to elicit a paracrine effect on coronary vascular smooth muscle, thus opposing the vasoconstricting effects of other anaphylactic mediators. (ahajournals.org)
  • BK induces vasodilatation and improved microvascular permeability results that partly are mediated from the supplementary release of additional mediators (for example nitric oxide and platelet activating element) via activation of BK receptors from the vascular endothelium. (87paydays.info)
  • Bradykinin dilates blood vessels via the release of prostacyclin, nitric oxide, and Endothelium-Derived Hyperpolarizing Factor. (diff.org)
  • Abstract Kinins acting on the B 2 receptor appear to be involved in the cardioprotective effect of preconditioning on myocardial ischemia/reperfusion injury. (ahajournals.org)
  • Previous studies in newborns of relatively altricial species, including rats and mice, provided evidence that various components of the renal kallikrein-kinin system are developmentally regulated ( 2 , 4 , 8 , 19 ). (physiology.org)
  • Studies by El-Dahr and Chao ( 6 ) also showed that the transition from newborn to adult life in rats is associated with six- and fourfold increases in renal kallikrein content and its mRNA and that B 2 mRNA levels are 30- to 40-fold higher in newborn than adult kidneys ( 31 ). (physiology.org)
  • Hypertensive patients, and spontaneously hypertensive rats, excrete less kallikrein than normal subjects, irrespective of races, and become salt-sensitive. (mdpi.com)
  • We conclude that bradykinin generation is involved in the PNV-induced pleural leukocyte migration in rats, where it can directly activate sensory nerves contributing to a neurogenic inflammatory mechanism. (unifesp.br)
  • DME vitreous containing relatively high levels of PKal and low VEGF induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. (nih.gov)
  • By inducing BK (bradykinin)-stimulated adrenomedullary catecholamine release, bolus injection of the β-fragment of activated plasma coagulation Factor XII (β-FXIIa) transiently elevates BP (blood pressure) and HR (heart rate) of anaesthetized, vagotomized, ganglion-blocked, captopril-treated bioassay rats. (portlandpress.com)
  • Previous studies have shown that the KKS is involved in glucose management by stimulating GLUT4 translocation ( 13 ), improving insulin stimulation of GLUT4 ( 14 ), and preventing dephosphorylation of insulin receptor substrate-1 ( 15 ). (diabetesjournals.org)
  • Renal kallikrein secretion is accelerated by potassium and ATP-sensitive potassium (K ATP ) channel blockers, such as PNU-37883A. (mdpi.com)
  • AIM: To investigate the system for bradykinin (BK) to stimulate intestinal secretomotor neurons and intestinal chloride secretion. (technumber.com)
  • Outcomes claim that BK stimulates neurogenic chloride secretion in the guinea pig Abacavir ileum by activating B2 receptors on secretomotor neurons activating cyclooxygenase-1 and stimulating PGE2 creation. (technumber.com)
  • 10 In human plasma, we have shown that BK is metabolized mainly by 3 metallopeptidases: ACE, aminopeptidase P (APP), and kininase I. ACE and APP are the first and second main inactivating pathways of BK, respectively. (ahajournals.org)
  • This tPA-triggered generation of bradykinin could participate in the deleterious effects of thrombolysis and is a potential target to improve neurological outcome in tPA-treated patients. (frontiersin.org)
  • Inhibition of bradykinin formation by novel agentscan provide targeted therapeutic approaches that address the pathophysiologic abnormalities. (chaen-rcah.ca)
  • specifically, whether the protease can bind to, cleave, internalize, and/or activate a fusion protein composed of the rabbit B 2 receptor conjugated to the green fluorescent protein (B 2 R-GFP). (ahajournals.org)
  • Both bradykinin receptor genes have been cloned in human and various species and the hydrophobicity prediction for the residues indicates that both bradykinin B1 and B2 receptors have seven helix transmembrane domains, a structure common to other members of the rhodopsin superfamily of G-protein-coupled receptors (Gq/11 and Gi). (phdify.com)
  • The amino acid sequence of the human B1 receptor (353 amino acid protein) is only 36% identical to the amino acid sequence (364 amino acid protein) of the human B2 receptor (12). (phdify.com)
  • The biological actions of BK are mediated by at least two major G-protein-coupled BK receptors termed Bl and B2. (allindianpatents.com)
  • The main transduction mechanism is through G-protein coupled receptors. (pharmainfo.net)
  • B2 Receptors- These are also G-protein coupled receptors and have multiple transduction events. (pharmainfo.net)
  • Burch, R.M., and Axelrod, J., 1987, Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: Evidence for G protein regulation of phospholipase A2, Proc. (springer.com)
  • Increased gluconeogenesis was accompanied by increased hepatic mRNA expression of Paclitaxel clinical trial forkhead box protein 01 (FoxO1, four-fold), peroxisome proliferator-activated receptor gamma co-activator 1-alpha (seven-fold), phosphoenolpyruvate carboxykinase (PEPCK, three-fold) and glucose-6-phosphatase (eight-fold). (fxr-agonists.com)
  • and (2) kinins acting via the B 2 receptor play an important role in the cardioprotective effect of ACEi and AT 1 -ant. (ahajournals.org)
  • 10 The elevation of bradykinin is thought to be self-limiting, with reported decreases of 93% upon withdrawal of ACEI therapy. (uic.edu)