Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determining the relationships between conformation and biological activity in peptide hormones and neurotransmitters is an important goal of contemporary biology. A major difficulty in these studies is the conformational flexibility of most peptides and the high dependence of the conformations on environment. The question arises whether conformations determined in solution are relevant to those important to the peptide at the membrane receptor(s). One recent approach to overcome these difficulties has been the use of conformational constraints by covalent bonding of side chain groups of residues in the peptide. In this manner linear peptides are rendered cyclic, and cyclic peptides are further conformationally constrained either by ring contractions or by other conformational constraints. Biologically active peptides specifically designed by this approach have been found to possess several useful properties including: 1) greater conformational integrity; 2) increased agonist or antagonist potency; 3) prolonged biological activity; 4) increased enzymatic stability; and 5) increased specificity for a particular receptor. Careful applications of this approach have provided important new designs features for peptide structure-function studies, and new insights into peptide conformation-activity relationships for oxytocin, somatostatin, enkephalin, bradykinin, vasopressin, and other biologically active peptides.
 ...
PMID:Conformational restrictions of biologically active peptides via amino acid side chain groups. 612 94

Direct binding of 125I-Tyr8-bradykinin to a microsomal fraction prepared from rat uterine smooth muscle, showed an apparent dissociation constant (KD) at 29 degrees C of 5.0 X 10(-10) M calculated from kinetic studies and 6.6 X 10(-10) M from Scatchard plot analysis. The binding of 125I-Tyr8-bradykinin was reversible and saturable, and demonstrated high specificity for Tyr8-bradykinin, bradykinin and Lys-bradykinin, but was not displaced by unrelated peptides angiotensin I, angiotensin II, Arg8-vasopressin and oxytocin. The binding sites were copurified by differential centrifugation and on a discontinuous sucrose density gradient with 5'-nucleotidase activity, a plasma membrane marker enzyme. Prolonged intravenous infusion of bradykinin (5 nmol/h for 2 days) induced a 20% decrease in the number of bradykinin binding sites without a change in the equilibrium dissociation constant. The present results demonstrate that receptors mediating the effect of bradykinin on rat uterine smooth muscle are situated on plasma membranes and the regulation of the receptors is in part under the control of endogenous bradykinin levels.
 ...
PMID:Bradykinin receptors in rat uterine smooth muscle: studies using radiolabeled ligand binding. 615 Dec 67

In vitro studies were undertaken to determine the reactivity and contractility of the rat main pulmonary artery (RPA) to some selected vasoactive agents. Oxytocin was found to be inactive RPA exhibited a poor responsiveness to vasopressin, acetylcholine, histamine, and bradykinin. Prostaglandins B2 and E2, K+, angiotensin, sympathomimetic agents (epinephrine and isoproterenol), 5-hydroxytryptamine (5-HT), and [Ca2+]0 were found to produce, consistently, potent and concentration-related contractions of the RPA. Pulmonary arterial strips that were precontracted with 5-HT responded with relaxations to isoproterenol in low concentrations and with contractions in high concentrations. Blockade of isoproterenol-induced relaxation by propranolol provides evidence for the existence of specific beta-adrenoceptors in RPA. The selective antagonism of contractile responses induced by epinephrine, 5-HT, acetylcholine, and histamine by phentolamine, methysergide, atropine, and pyrilamine, respectively, provides evidence for the occurrence of specific alpha-adrenergic, "D"-serotonin as well as some cholinergic (muscarinic) and H1-histamine receptors in the RPA.
 ...
PMID:Reactivity and contractility of rat main pulmonary artery to vasoactive agents. 625 36

Cells having morphological and histochemical properties of collecting tubules were isolated from rabbit renal papillae. Confluent monolayer cultures of these renal papillary collecting tubule (RPCT) cells formed hemicysts and adhered with morphological asymmetry to Millipore filters. Cultures of 1-day-old RPCT cells synthesized cAMP in response to arginine vasopressin (AVP) (half-maximal response to 10(-10) M), oxytocin, and parathyroid hormone (half-maximal responses at 5 X 10(-9) M) but not to adrenergic agents. After 10 days of growth (fourfold increase in cell number) RPCT cells retained the same pattern of histochemical and hormonal responses as 1-day-old cells. Hormones were tested for their influence on the release of immunoreactive prostaglandins (iPG) by RPCT cells; the major product under both basal and stimulated conditions was iPGE2. At very low concentrations (greater than or equal to 10(-10) M), bradykinin, lysyl-bradykinin, and methionyl-lysyl-bradykinin caused four- to sixfold increases in the rate of iPGE2 formation within 3 min; smaller (less than twofold) increases were observed with relatively high concentrations of epinephrine (10(-5) M), norepinephrine (10(-5) M), and angiotensin II (10(-7) M), but only after longer incubations. Significantly, neither AVP (10(-7) M) nor [deamino]AVP (10(-7) M) caused prostaglandin release by RPCT cells. Our results indicate that kinins can act directly on the collecting tubule to elicit PGE2 formation; furthermore, this effect of kinins may be natriuretic, since PGE2 has been shown to inhibit Na+ resorption by the medullary collecting tubule and thick ascending limb.
 ...
PMID:Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. 626 8

125I-angiotensin II (125I-AII) binding was examined in the hypothalamic-thalamic-septal-midbrain (HTSM) region of HLA-Wistar rats in the presence of CNS-active agents. Angiotensin I, II, and III and saralasin competed for 125 I-AII binding, whereas structurally unrelated peptides such as arginine and lysine vasopressin, oxytocin, LHRH, TRH, bradykinin, and substance P did not. In contrast, ACTH and neurotensin exhibited a weak, dose-dependent competition for 125 I-AII binding. The relative potencies of AII, AI, neurotensin and ACTH were 100:1:0.1:0.05, respectively. Neurotensin and ACTH competition was not additive with AII suggesting interaction at shared binding sites. Most importantly, a wide variety of other CNS active agents such as methyldopa, naloxone, catecholamines, clondidine, and reserpine, failed to inhibit 125 I-AII binding, thus further defining the specificity of the CNS AII receptor.
 ...
PMID:The specificity of angiotensin II receptor binding in rat brain. 627 72

The brain contains a large variety and number of peptides some of which were known earlier as hypothalamic hormones (vasopressin, oxytocin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, somatostatin) or as pituitary hormones (the family of opiomelanocortins), while others, not primarily known as hypothalamic or pituitary hormones, may also have endocrine effects (substance P, angiotensin II, neurotensin, bombesin, vasoactive intestinal peptide (VIP), gastrin-cholecystokinin, glucagon, carnosine, bradykinin). These peptides, which form a new class of putative neurotransmitters, are present early in brain development and show important sex differences in both their pattern of innervation and their effects. Their peripheral effects may include intrauterine growth of the placenta and fetus, the timing of birth, acceleration of the course of labour and responses to haemorrhage (redistribution of cardiac output and stimulation of blood cell formation). Endogenous peptides are probably involved in brain development, which may explain their general, permanent and sex-dependent effects when given in the period of rapid brain development. Although peptides might in the future be useful for stimulating recovery from retarded brain development, at present one should be aware of the potential dangers of their use in, for example, obstetrics.
 ...
PMID:Development of peptidergic systems in the rat brain. 627 64

A post-proline cleaving enzyme [prolyl endopeptidase, EC 3.4.21.26] was purified about 3,700-fold from an extract of bovine brain by a series of column chromatographies on DEAE-Sephadex, hydroxyapatite and PCMB-T-Sepharose, and gel filtration on Sephadex G-200 using N-carbobenzoxy-Gly-Pro-beta-naphthylamide (Z-Gly-Pro-2-NNap), thyrotropin releasing hormone (TRH) and oxytocin as substrates. The purified enzyme appeared homogeneous as judged by disc gel and SDS gel electrophoreses. The enzyme was most active at pH 7.5 and 7.2 with Z-Gly-Pro-2-NNap and TRH, respectively, and hydrolyzed peptide bonds involving Pro-X (X=amino acid, peptide, ester and amide) bonds of synthetic substrates, oxytocin, vasopressin, neurotensin, substance P, tuftsin, bradykinin, and insulin B chain. However, the enzyme was inert toward collagen, gelatin, and casein. The enzyme was completely inactivated by diisopropylphosphorofluoridate (DFP), Z-Gly-Pro-chloromethyl ketone and p-chloromercuribenzoate (PCMB), while it was not inhibited by phenylmethane sulfonylfluoride (PMSF) or metal chelators. Determination of the amino acid composition revealed that the enzyme contained 25 half-cystines. Modification of three cysteine residues of the enzyme by PCMB led to complete inactivation. The isoelectric point of the enzyme was 4.8, and the molecular weight was estimated to be 76,000 by ultracentrifugal analysis and 75,000-74,000 by both gel filtration and sodium dodecyl sulfate (SDS) gel electrophoresis, suggesting that the enzyme is present as a monomer. These results indicate that the post-proline cleaving enzyme from bovine brain is very similar to those previously purified from lamb brain and kidney in its enzymatic properties, substrate specificity and physicochemical properties, in sharp contrast with the results obtained by Tate, who reported that the bovine brain prolyl endopeptidase was inert toward oxytocin, vasopressin and bradykinin.
 ...
PMID:Post-proline cleaving enzyme (prolyl endopeptidase) from bovine brain. 636 Oct 10

Levels of prekallikrein and HMW kininogen that had increased during pregnancy decreased with start of labor. The role of the kinin-forming system with oxytocin in the mechanism of labor was suggested from the results of decreased prekallikrein and HMW kininogen, appearance of a free kallikrein-like enzyme during labor, and from the case of arrested labor in which both prekallikrein and HMW kininogen were markedly decreased. Prekallikrein was markedly decreased in patients with acute obstetrical DIC and severe toxemia of pregnancy. The excessive activation of prekallikrein in DIC seemed to be of help for understanding such clinical signs as shock, abnormal labor, and increased permeability in obstetrical DIC.
 ...
PMID:The kinin-forming enzyme system in pregnancy and obstetrical DIC. 642 Dec 72

A sensitive and specific radioimmunoassay for measuring urinary kinins was developed. Antibodies against bradykinin were induced in rabbits by injecting bradykinin coupled to bovine albumin. One of the antisera generated was used at a final dilution of 1:18,000 to obtain a 30% total binding of bradykinin-(8-tyrosine)-[125I]-triacetate. Synthetic bradykinin (5-1,000 pg) was used as standard in the curves. The sensitivity of the assay was 5 pg. The recovery of bradykinin added to urinary samples was 86.85 +/- 6%. The intraassay and interassay coefficients of variation were 3.3% (n = 12) and 4.4% (n = 5), respectively. The antiserum showed no cross-reactivity with oxytocin or low molecular weight kininogen and cross-reacted with kallidin (lys-bradykinin), met-kallidin, and angiotensin I, but cross-reaction with angiotensin I (2.5%) was low enough to be disregarded. The mean urinary levels of total kinins in 12 normal subjects were 23.2 +/- (SEM) 2.2 micrograms/day.
 ...
PMID:A radioimmunoassay method for measurement of urinary kinins. 648 28

A bovine brain thyrotropin-releasing-factor (thyroliberin) deamidase has been purified 1100-fold to apparent homogeneity. Molecular weight estimates by gel filtration and sodium dodecylsulfate gel electrophoresis indicate that the enzyme consists of a single polypeptide chain of molecular weight of about 62 000-65 000. The enzyme is inactivated by sulfhydryl blocking agents. Serine proteinase inhibitors, phenylmethanesulfonyl fluoride and benzamidine, have no effect. Besides thyroliberin, the enzyme hydrolyzes peptide bonds involving the carboxyl group of proline residues in luliberin, tuftsin, angiotensin II, melanotropin, and neurotensin. Oxytocin, vasopressin, and bradykinin are not cleaved; they are, however, strong competitive inhibitors of thyroliberin deamidation. The specificity studies indicate that the enzyme is a "post-proline cleaving enzyme" which hydrolyzes peptides of the general structure, Yaa-Pro-Xaa, in which Xaa = amino acid, peptide, or amide (not Pro), and Yaa = N-blocked basic amino acid or a peptide sequence in which the C-terminal residue (i.e. the residue prior to Pro) is a basic amino acid such as His, Lys, or Arg. The enzyme is compared to other post-proline cleaving enzymes.
 ...
PMID:Purification and properties of a bovine brain thyrotropin-releasing-factor deamidase. A post-proline cleaving enzyme of limited specificity. 679 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>