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

A technique has been developed for prelabelling and permeabilisation of guinea pig uterine myocytes to enable measurement of arachidonic acid release/phospholipase A2 activity in cells with intact membranes. Intact cells were prelabelled with [3H]inositol or [3H]arachidonic acid for measurement of phospholipase C and A2 respectively. In intact cells 10 nM endothelin-1 or 1 microM bradykinin stimulated both inositol polyphosphate and arachidonic acid release, whilst 1 microM oxytocin, arginine vasopressin or histamine were without effect. In Streptolysin-O permeabilised myometrial cells calcium-stimulation of inositol polyphosphate and arachidonic acid release was detected between 10 microM and 1 mM free calcium. The patterns of inositol polyphosphate and arachidonic acid release were broadly similar. Responses to 1 mM calcium were not detected in intact cells not treated with Streptolysin-O. For arachidonic acid release the K0.5 for calcium activation was about 7 microM, a level above that normally likely to be found in the uterine myocyte. Hence it is concluded that unless there are high local concentrations of calcium close to the plasma membrane, calcium is unlikely alone to be the primary regulator of arachidonic acid release and phospholipase A2.
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PMID:Measurement of arachidonic acid release from permeabilised myometrial cells of guinea pig uterus. 130 78

Our study showed that there were statistically significant correlations between the systolic and diastolic ratio (S/D) of maternal uterine or umbilical artery and the levels of maternal serum aminopeptidase activities in pre-eclampsia. Kininase I was positively correlated with the S/D ratios, whereas placental leucine aminopeptidase (P-LAP) and aminopeptidase A were negatively correlated with the S/D ratios. It is known that the increased S/D ratios reflect the increased utero-placental blood flow resistance. Since our previous study showed that placental aminopeptidases degrade vasoactive peptides such as oxytocin, angiotensin and bradykinin, which the fetus actively produces, our present study suggests that the increased vascular resistance in feto-placental circulation in pre-eclampsia is partly controlled by changes in vaso-active peptides, via degradation by placental aminopeptidases.
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PMID:Relationship between the changes in placental blood flow resistance assessed by Doppler technique and maternal serum placental aminopeptidases, which degrade vaso-active peptides, in pre-eclampsia. 151 91

Oxytocin, bradykinin, melittin and A23187 increased cyclic GMP levels through activation of soluble guanylate cyclase in cultured porcine kidney epithelial cells, LLC-PK1. NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide formation, decreased both basal and stimulated levels of cyclic GMP in a concentration-dependent manner. L-Arginine, but not D-arginine, augmented basal as well as stimulated levels of cyclic GMP and prevented the inhibition induced by NG-monomethyl-L-arginine. Similar effects of L-arginine were also observed with L-argininamide, L-arginine ethyl ester, L-arginine methyl ester and the dipeptide L-arginyl-L-aspartic acid. NG-monomethyl-L-arginine did not affect cyclic GMP accumulation induced by sodium nitroprusside, an activator of soluble guanylate cyclase, and atrial natriuretic factor, an activator of particulate guanylate cyclase. Stimulatory effects of oxytocin, glyceryl trinitrate, sodium nitroprusside, bradykinin, melittin and A23187 on cyclic GMP accumulation were enhanced with superoxide dismutase and diminished with oxyhemoglobin. However, atrial natriuretic factor-induced cyclic GMP accumulation was not affected. Furthermore, endothelium derived relaxing factor-like activity was detected in the conditioned medium from LLC-PK1 cells stimulated with oxytocin. Based on these data, we conclude that endothelium-derived relaxing factor is produced in this cell type and participates in the regulatory mechanism of cyclic GMP formation as an intra- and intercellular messenger for activation of soluble guanylate cyclase.
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PMID:Formation of endothelium-derived relaxing factor in porcine kidney epithelial LLC-PK1 cells: an intra- and intercellular messenger for activation of soluble guanylate cyclase. 167 Oct 98

The actions of hydroalcoholic and tea extracts of stems of Leonotis nepetaefolia on agonist-induced and electrically-evoked contractions have been analysed in-vitro in rat uterus and left atrium and in guinea-pig ileum and trachea. The tea extract (500-2000 micrograms mL-1) caused parallel and graded rightward shifts of concentration-response curves to bradykinin and BaCl2 in the rat isolated uterus, but antagonized responses to prostaglandin F2 alpha in a typically non-competitive manner. The hydroalcoholic extract also caused rightward displacements of the curves to bradykinin, acetylcholine (ACh), angiotensin II, oxytocin and BaCl2 and reduced their maximal contractile effects. Both extracts (30-3000 micrograms mL-1) relaxed uterine preparations precontracted with KCl (80 mM), the hydroalcoholic extract being about 2-fold more potent than the tea extract. The relaxant response to the former was unaffected by propranolol (1 microM) or forskolin (10 nM), but was potentiated 2-fold by 3-isobutyl-1-methylxanthine (10 microM). In the guinea-pig ileum the hydroalcoholic extract shifted the ACh- and bradykinin-induced contractile curves to the right and markedly inhibited their maximal effects, whereas the tea extract caused a typical non-competitive antagonism of ACh-induced contractile responses. In field-stimulated ileal strips, both extracts (3-3000 micrograms mL-1) caused contractions and inhibited twitch responses. Guinea-pig tracheal rings precontracted with carbachol (0.3 microM) were relaxed only by concentrations of either extract in excess of 1000 micrograms mL-1, an action that was unaffected by propranolol (0.1 microM) or by offomethacin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of crude extracts from Leonotis nepetaefolia (Labiatae) on rat and guinea-pig smooth muscle and rat cardiac muscle. 168 Oct 66

We discovered an enzyme in human platelets that deamidates substance P and other tachykinins. Because an amidated carboxyl terminus is important for biological activity, we purified and characterized this deamidase. The enzyme, released from human platelets by thrombin, was purified to homogeneity by ammonium sulfate precipitation, followed by chromatography on an octyl-Sepharose column and chromatofocusing on PBE 94. The purified enzyme exhibits esterase, peptidase, and deamidase activities. The peptidase activity (with furylacryloyl-Phe-Phe) is optimal at pH 5.0 while the esterase (benzoyl-tyrosine ethyl ester) and deamidase (D-Ala2-Leu5-enkephalinamide) activities are optimal at pH 7.0. With biologically important peptides, the enzyme acts both as a deamidase (substance P, neurokinin A, and eledoisin) and a carboxy-peptidase (with bradykinin, angiotensin I, substance P-free acid, oxytocin-free acid) at neutrality, although the carboxypeptidase action is faster at pH 5.5. Enkephalins, released upon deamidation of enkephalinamides, were not cleaved. Gly9-NH2 of oxytocin was released without deamidation. Peptides with a penultimate Arg residue were not hydrolyzed. Some properties of the deamidase are similar to those reported for cathepsin A. The deamidase is inhibited by diisopropylfluorophosphate, inhibitors of chymotrypsin-type enzymes, and mercury compounds while other inhibitors of catheptic enzymes, trypsin-like enzymes, and metalloproteases were ineffective. In gel filtration, the native enzyme has an Mr = 94,000 while in non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis the Mr = 52,000 indicating it exists as a dimer. After reduction, deamidase dissociates into two chains of Mr = 33,000 and 21,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. [3H]diisopropylfluorophosphate labeled the active site serine in the Mr = 33,000 chain. The first 25 amino acids of both chains were sequenced. They are identical with the sequences of the two chains of lysosomal "protective protein" which, in turn, has sequence similarity to the KEX1 gene product and carboxypeptidase Y of yeast. This protective protein complexes with beta-galactosidase and neuraminidase in lysosomes and is vitally important in maintaining their activity and stability. A defect in this protein is the cause of galactosialidosis, a severe genetic disorder. The ability of physiological stimuli (e.g. thrombin or collagen) to release the deamidase from platelets indicates that it may also be involved in the local metabolism of bioactive peptides.
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PMID:A peptidase in human platelets that deamidates tachykinins. Probable identity with the lysosomal "protective protein". 169 76

Cross-reaction of a rat monoclonal antibody (BTP-1) against seventeen substance P analogues was studied. The antibody was of IgG type and related to the carboxyl terminal of substance P, especially methionyl in the terminal, but did not depend on the strength of antagonistic effects of these analogues. It did not show cross-reaction with the following nine peptides: glucagon, endorphin, angiotensin I, II, leucine-enkephalin, methionine-enkephalin, bradykinin, oxytocin and dernorthin, indicating its high specificity to substance P. By means of immuno-enzyme histochemical method, it was shown that stained nerve fibers were located in the gelaliternous substance of Rolando, interpeduncular nucleus, substantia nigra and nerve cell bodies in the vestibular nucleus, lateral tegmental nucleus of mesencephalon and ventral region of third ventricle.
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PMID:[Study of characteristics of monoclonal antibody against substance P]. 169 64

In order to study the effects of peptides on intrinsic cardiac neurons, substance P, bradykinin, oxytocin, calcitonin gene related peptide, atrial natriuretic peptide and vasoactive intestinal peptide were administered into canine atrial or ventricular ganglionated plexi. When substance P was injected into right atrial or cranial medial ventricular ganglionated plexi heart rate, atrial force and ventricular intramyocardial pressures were augmented. No cardiac changes occurred when similar volumes of saline (i.e., peptide vehicle) were injected into these ganglionated plexi. When bradykinin was injected into atrial or ventricular ganglionated plexi heart rate, atrial force and ventricular force were augmented in approximately 50% and depressor responses were elicited in approximately 50% of these animals. When oxytocin was injected into right atrial ventral ganglionated plexi heart rate and atrial forces were reduced in five of ten dogs studied. No cardiac changes occurred when oxytocin was injected into left atrial or ventricular ganglionated plexi. No responses were elicited when calcitonin gene related peptide, atrial natriuretic peptide or vasoactive intestinal peptide was administered into atrial or ventricular ganglionated plexi. Following acute decentralization of the heart, no significant responses were elicited by repeat administrations of substance P, bradykinin or oxytocin, implying that connectivity with central nervous system neurons was necessary for consistent responses to be elicited. It is concluded that substance P, bradykinin and oxytocin can affect neurons on the heart such that cardiodynamics are modified, these different peptides eliciting different cardiac responses.
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PMID:Cardiac responses elicited by peptides administered to canine intrinsic cardiac neurons. 170 Mar 99

Endothelins 1, 2 and 3 (ET-1, ET-2 and ET-3; 1-30 nM) caused long-lasting concentration-dependent tonic contractions of uterine strips from non-pregnant rats. The potency of ET-1 (EC50 7 nM) was similar to that of angiotensin II (AII) and greater than that of ET-2 or ET-3 (EC50S greater than or equal to 10 nM), bradykinin, Bay K 8644, oxytocin (OT), 5-hydroxytryptamine, prostaglandin F2 alpha (PGF2 alpha) or acetylcholine. Strips from 21-day pregnant rats were 2- to 3-fold more sensitive to ET-1, AII, OT and PGF2 alpha and 200-fold more sensitive to Bay K 8644 than non-pregnant preparations. The development of tonic responses to ET-1 (30 nM) and of phasic-rhythmic ones to Bay K 8644 (300 nM) was fully prevented in strips from non-pregnant rats bathed in Ca2(+)-free medium, but stepwise reintroduction of Ca2+ (0.03-3 mM) to the solution allowed the manifestation of contractions in response to both agonists. Responses to ET-1 required less Ca2+ than those to Bay K 8644. Strips challenged with ET-1 while in Ca2(+)-free medium developed greater contractions upon reintroduction of Ca2+ than preparations stimulated with the peptide in normal medium. The reverse occurred with Bay K 8644-induced contractions. Nicardipine (10 nM) abolished the responses of strips from non-pregnant rats to Bay K 8644 (300 nM), but only attenuated ET-1-induced (30 nM) contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of endothelins, Bay K 8644 and other oxytocics in non-pregnant and late pregnant rat isolated uterus. 171 Jan 86

1. The effects of 5 pregnane compounds isolated from the rhizomes of Mandevilla illustris were examined against bradykinin (BK), Lysyl-bradykinin (L-BK), acetylcholine (ACh) and oxytocin (Ot)-induced contractions in the isolated uteri of the rat. 2. Compounds MI 15 and MI 18 (5-40 micrograms/ml) caused a parallel and concentration-dependent rightward displacement of BK and L-BK concentration-response curves. Compound MI 21 (2.5-10 micrograms/ml) also produced a concentration-dependent displacement to the right of the BK concentration-response curve, but reduced its maximal response. Schild analysis of these data were linear (r close to 1) and furnished the following PA2 values (as G/ml): 6.0, 5.1 and 5.9, respectively. However, the slopes were significantly higher than unity. Compounds MI 25 and MI 27 (10-40 micrograms/ml) caused little or even no effect against BK and ACh responses. 3. In addition, compounds MI 18 and MI 21 (10-40 micrograms/ml) also antagonized in a concentration-dependent manner L-BK concentration-response curves. Schild plot were linear (r close to 1) and yielded the nominal pA2 values (as G/ml) of 5.0 and 5.8, respectively, but the slopes were significantly different from one. 4. Like the results obtained previously with the crude extract from M. illustris, the purified compounds from the rhizome of this plant were not selective towards kinin action since at the same range concentrations they markedly interfered with both the sensitivities and the maximal responses caused by ACh and Ot in this preparation.
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PMID:Action of pregnane compounds from Mandevilla illustris against contractions induced by kinins and other oxytocics in the rat isolated uterus. 181 Aug 5

From a series of potent cyclic hexapeptide oxytocin (OT) antagonists, a compound that exhibited significant bradykinin (BK) agonist activity was identified. L-366,811 (cyclo[L-proline-D-tryptophan-L-isoleucine-D-pipecolic acid-L-piperazine-2-carboxylic acid-N-Me-D-phenylalanine]) stimulated phosphatidylinositol (PI) turnover in rat uterine slices in vitro (approximately EC50, 2 microM) with a maximal effect (15-fold increase over basal) greater than that obtained for either BK or OT. L-366,811 also elicited dose-related contractions of the isolated rat uterus, producing measurable effects at 100 nM. Several other equally potent OT antagonists from the cyclic hexapeptide structural class were either less potent or inactive as activators of uterine PI turnover or contractility. The stimulatory effects of L-366,811 on uterine PI turnover and contractions were blocked by BK antagonists but not by an arginine vasopressin (AVP)/OT antagonist. In radioligand binding studies, L-366,811 exhibited moderate affinity (IC50, 360 nM) for the [3H]BK binding site in rat uterus, consistent with its potency in the functional models. These results indicate that L-366,811 exhibits BK agonist activity in rat uterus in vitro.
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PMID:Bradykinin agonist activity of a novel, potent oxytocin antagonist. 189 11


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