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)

Bradykinin, oxytocin, physalaemin and some autonomic drugs were injected in to the common carotid artery. Physalaemin evoked secretion and a pressure rise in the submaxillary duct. A duct pressure rise could be elicited by bradykinin which did not evoke secretion. Autonomic blocking agents did not diminish secretion evoked by physalaemin and did not change pressure responses elicited by bradykinin or physalaemin. Neither secretion, nor duct pressure changes could be recorded after administration of oxytocin. In agreement with previous experiments secretion evoked by autonomic drugs was found to be mediated via cholinergic, alpha- and beta-adrenergic receptors, while motor effects were due to activation of cholinergic and alpha-adrenergic receptors.
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PMID:Secretory and motor effects in the submaxillary gland of the rat on intraarterial administration of some polypeptides and autonomic drugs. 96 45

The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.
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PMID:Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin. 217 99

Bradykinin (BK) (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) was degraded by rat brain synaptic membranes at a rate comparable to that found for Met-enkephalin, but approximately 40 times the rate for vasopressin and oxytocin. The catabolic pathway for BK and its metabolites was elucidated through the use of high performance liquid chromatography for metabolite identification and peptidase inhibitors for blocking specific cleavage sites. BK was hydrolyzed at three sites: at the -Phe5-Ser6- bond by metalloendopeptidase 24.15, at the -Pro7-Phe8- bond by an apparently novel peptidyl dipeptidase, and at the -Phe8-Arg9 bond by a carboxypeptidase B-like enzyme. Each enzyme contributed about equally to BK degradation under the assay conditions used. Some of the resulting metabolites were further hydrolyzed: BK(1-8) to BK(1-7) + Phe by a DFP inhibitable prolyl carboxypeptidase-like enzyme, BK(1-8) to BK(1-5) + BK(6-8) by metalloendopeptidase 24.15, BK(1-7) slowly to BK(1-5) by a second peptidyl dipeptidase which was captopril inhibited, and Phe-Arg to Phe + Arg by a bestatin-inhibited dipeptidase. A number of properties of the individual enzymes were determined including sensitivity to a variety of peptidase inhibitors. These results provide a starting point for investigating the potential physiological role of each enzyme in BK function in the brain.
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PMID:Degradation of bradykinin and its metabolites by rat brain synaptic membranes. 260 54

Binding of [3H]oxytocin to purified myometrial plasma membranes was unaffected by continuous infusion of bradykinin over 5 days in rats pretreated with oestradiol 2 days before collection of tissue. In contrast, oxytocin treatment resulted in a 76% decrease in maximal binding of [3H]oxytocin and thereby in oxytocin receptor concentration without affecting the dissociation constant. The KM value (molar concentration giving half maximal contraction) of isolated uterine strips stimulated with oxytocin was increased and maximal contractile responses were reduced following oxytocin infusions. The binding of [3H]bradykinin to purified plasma membranes was influenced by treatment with both oxytocin and bradykinin. Bradykinin infusions down-regulated the bradykinin receptor concentration by 19%, while the receptor affinity remained unchanged. Maximal contraction (Emax) values of isolated strips stimulated with bradykinin exhibited a slightly attenuated response and KM values were significantly enhanced. Long-term treatment with oxytocin down-regulated myometrial bradykinin receptors by 31%. In addition, oxytocin infusions caused Emax to decrease and KM to increase in experiments with isolated uterine strips stimulated with bradykinin. It is concluded that the down-regulation of oxytocin and bradykinin receptors following prolonged exposure to oxytocin may result from changes in a common pathway for intracellular peptide receptor processing. Likewise, the increased KM values of isolated myometrial strips (despite unchanged dissociation constants) suggest that prolonged oxytocin treatment affects the coupling between receptor activation and contractile response.
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PMID:Receptor-binding characteristics and contractile responsiveness of the myometrium following prolonged infusion of bradykinin and oxytocin in rats. 284 29

Neuropeptides and biogenic amines known to be present in neurons or afferent terminals in the paraventricular nucleus (PVH), supraoptic nucleus (SON) and/or lateral hypothalamus (LH) were added to small areas of these structures obtained by micropuncture and cyclic adenosine monophosphate (cAMP) levels were measured. cAMP accumulation occurred in PVH, SON and LH in response to neuropeptides of the secretin family, such as vasoactive intestinal peptide (VIP) and in response to catecholamines. Bradykinin, alpha-melanocyte-stimulating (alpha-MSH), luteinizing hormone-releasing hormone (LH-RH), oxytocin and carbamylcholine stimulated cAMP accumulation selectively in one or two of the above structures. Glucagon, cholecystokinin (CCK), somatostatin (SRIF), corticotropin-releasing factor (CRF), thyrotropin-releasing hormone (TRH), adrenocorticotropin (ACTH), melanocyte-stimulating hormone (MSH), methionine enkephalin (Met-Enk), beta-endorphin, neurotensin, bombesin and angiotensin II did not effect cAMP levels while leucine enkephalin (Leu-Enk), arginine vasopressin and gamma-aminobutyric acid (GABA) elicited regionally selective decreases in basal levels of cAMP. When interactions between some of these compounds were measured, VIP and norepinephrine exerted a more than additive effect on cAMP elevation in the PVH, while the effect on cAMP of the SON and LH was additive.
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PMID:Interaction of neuropeptides and biogenic amines on cyclic adenosine monophosphate accumulation in hypothalamic nuclei. 300 57

The present study examines the relaxant selectivity of endothelium-derived relaxing factor (EDRF) released from cultured endothelial cells. Endothelial cells from bovine pulmonary artery (CCL-209) in culture were grown on Cytodex-3 microcarrier beads, packed into a column and superfused to release EDRF. EDRF response was estimated by its ability to relax phenylephrine-contracted rings of rabbit aorta. Bradykinin and A23187 (10(-10) to 10(-6) M) caused dose-dependent release of EDRF from cultured bovine pulmonary artery endothelial cells. The release was dependent on endothelial cell number. A23187 caused a larger and longer-lasting release of EDRF than bradykinin. EDRF relaxation was selective for blood vessels. EDRF relaxed rabbit aortic rings, but it did not relax histamine-contracted guinea pig tracheal, rabbit taenia coli strips or oxytocin-contracted guinea pig uterine rings. These nonvascular smooth muscles were, however, relaxed by isoproterenol (10(-4) M) and sodium nitroprusside (SNP, 10(-5) M). The sensitivity of guinea pig aortic rings and tracheal strips to SNP were compared. The IC50 values for SNP (10(-9) to 10(-5) M) were 0.07 and 0.3 microM for aortic rings and tracheal strips, respectively. Although the tracheal strips were about 4-fold less sensitive than the aorta toward SNP, a complete relaxation was achieved. These results suggest that EDRF relaxes vascular smooth muscles but not respiratory, Gl or reproductive smooth muscles. Thus, EDRF may be a selective relaxant of vascular smooth muscle.
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PMID:Endothelium-derived relaxing factor is a selective relaxant of vascular smooth muscle. 349 4

The release of prostacyclin from chopped myometrial fractions of 18-20 day pregnant rats was assayed by inhibition of ADP-induced aggregation of citrated rabbit platelet-rich plasma. Preincubation of myometrial tissue with oxytocin 10 mU/ml increased prostacyclin generation from 2.25 +/- 0.48 (control) to 3.75 +/- 0.73 ng/mg over 15 minutes. Bradykinin 20 microgram/ml also caused a significant increase in myometrial prostacyclin output from 2.26 +/- 0.19 to 4.26 +/- 0.64 ng/mg. PGF2 alpha 1 microgram/ml did not increase prostacyclin release significantly. Pretreatment of myometrial tissue with the phospholipase inhibitor mepacrine significantly reduced the peptide-stimulated release of prostacyclin. The results suggest that prostacyclin production may play an important role in modulating the actions of oxytocin and bradykinin in the pregnant rat myometrium.
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PMID:Effects of uterine stimulant drugs on prostacyclin production by the pregnant rat myometrium. I. Oxytocin, bradykinin and PGF2 alpha. 699 22

Prolyl endopeptidase has been predominantly described as a cytosolic activity capable of cleaving a number of important neuropeptides (including TRH, LHRH, Bradykinin, Angiotensin, Substance P, Neurotensin, Oxytocin and Vasopressin) on the carboxy side of proline. In this paper, we report, for the first time, on the complete purification and characterization of a membrane-bound form of prolyl endopeptidase. This novel activity has been isolated from the synaptosomal (plasma membranes) membranes of bovine brain. Following gel filtration, hydroxylapatite and hydrophobic interaction chromatographies, the prolyl endopeptidase activity was purified 1400-fold with a 23% recovery of activity. The enzyme was shown to have a relative molecular mass of 87 kDa and a Km of 60 microM for its specific fluorimetric substrate, Z-GlyProMCA. The purified enzyme demonstrated a relatively broad substrate specificity and a relatively high affinity for proline-containing neuropeptides. It was shown to be inhibited by certain thiol-protease inhibitors and by the metal chelator, 1,10-phenanthroline, thus possibly classifying it as a 'thimet' activity. The purified particular form of proyl endopeptidase displayed a similar substrate specificity to the previously reported cytosolic forms of the enzyme. However, there were differences between the two forms in term of their sensitivity to inhibitors, their affinities for the peptide substrates and their relative molecular masses. The different subcellular location (i.e. the synaptosomal membrane) of the particulate prolyl endopeptidase is also of potential physiological significance given that here it is more likely to come in contact with the vesicle-bound neuropeptides than is its cytosolic counterpart.
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PMID:Purification and characterization of a novel membrane-bound form of prolyl endopeptidase from bovine brain. 902 55

Experiments were performed on uteri from estrogen-primed female rats. Bradykinin (BK) (10(-8) M) significantly augmented biosynthesis of prostaglandin F2 alpha (PGF2alpha) and prostaglandin E2 (PGE2), and this synthesis was completely blocked by NG-monomethyl L-arginine (NMMA) (300 microM), a competitive inhibitor of nitric oxide synthase (NOS). Blockade of prostaglandin synthesis by indomethacin caused rapid dissipation of isometric developed tension (IDT) induced by BK. Blockade of NOS with NMMA had similar but less marked effects. Combining the two inhibitors produced an even more rapid decay in IDT, suggesting that BK-induced NO release maintains IDT by release of prostanoids. The decline of frequency of contraction (FC) was not significantly altered by either indomethacin or NMMA but was markedly accelerated by combination of the inhibitors, which suggests that PGs maintain FC and therefore FC decline is accelerated only when PG production is blocked completely by combination of the two inhibitors of PG synthesis. The increase in IDT induced by oxytocin was unaltered by indomethacin, NMMA or their combination indicating that neither NO nor PGs are involved in the contractions induced by oxytocin. However, the decline in FC with time was significantly reduced by the inhibitor of NOS, NMMA, suggesting that FC decay following oxytocin is caused by NO released by the contractile process. In the case of PGF2alpha, NMMA resulted in increased initial IDT and FC. The decline in FC was rapid and dramatically inhibited by NMMA. Receptor-mediated contraction by BK, oxytocin, and PGF2alpha is modulated by NO that maintains IDT by releasing PGs but reduces IDT and FC via cyclic GMP.
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PMID:Nitric oxide in the contractile action of bradykinin, oxytocin, and prostaglandin F2 alpha in the estrogenized rat uterus. 938 Jul 57

The decapeptide kallidin-10, substance P and angiotensin increased the resistance of guinea-pig lungs to inflation; lysine- or arginine-vasopressin and oxytocin were inactive. Acetylsalicylate antagonized this action of kallidin-10, as it does that of bradykinin, but it failed to antagonize substance P or angiotensin. Bradykinin also increased resistance to inflation of rabbit lungs and, to a lesser extent, rat lungs. It caused a relatively slow contraction of guinea-pig tracheal and bronchial muscle in vitro, but it did not contract isolated rabbit, dog or human bronchus. The relative potencies of different substances on different bronchial test preparations, and also in different species, were not parallel.
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PMID:Actions of some peptides on bronchial muscle. 1386 45


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