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)

The exposure of WRK1 cells to arginine vasopressin (AVP), lysine vasopressin, or oxytocin for 18 h at 37 degrees C induced a homologous desensitization of the vasopressin- (VP) receptors. Dose-response curves of [3H]lysine vasopressin binding to control and desensitized WRK1 cells revealed a decrease in the maximal number of binding sites without any modification of its affinity (Kd values = 4.40 +/- 0.76 nM and 4.65 +/- 0.78 nM for control and desensitized conditions, respectively). The phenomenon was time- and dose-dependent. It was directly related to receptor occupancy, since the concentration of VP analogues leading to a half-maximal occupancy of VP receptors was closely related to the concentration of the corresponding analogue leading to a half-maximal decrease in VP-binding sites. It was also agonist-specific, since the V1 vasopressin antagonist desGly9d(CH2)5[D-Tyr(Et)2]VAVP was unable to affect the number of receptors. These desensitization processes were completely inhibited when the functional coated pits present in WRK1 cells were suppressed, indicating that the loss of VP-binding sites was related to receptor internalization. The exposure of WRK1 cells to a vasopressin agonist for 18 h also led to an inhibition of the vasopressin-sensitive phospholipase C activity. It was time- and agonist-dose-dependent, and occurred without any detectable changes in apparent affinity values (1.40 +/- 0.04 and 1.90 +/- 0.36 nM for control and desensitized cells, respectively). Control experiments showed that these inhibitions could not have been caused by a decrease in the labeling of inositol lipids. It is likely that they were mainly due to receptor internalization since (i) the hormonal treatment did not modify the basal level of phospholipase C; (ii) the maximal loss of VP-binding site was similar to the maximal inhibition of VP-stimulated IP accumulation; (iii) the recoveries of both VP-binding sites and VP-sensitive phospholipase C activity followed exactly the same time course (t1/2 = 4 h). In addition to this homologous desensitization of VP-sensitive phospholipase C activity, AVP also induced heterologous desensitization of bradykinin-sensitive phospholipase C activity. However, this effect was relatively weak (maximal inhibition 17 +/- 3%). The time course of VP-sensitive phospholipase C desensitization was more rapid than that of VP-receptors, indicating that desensitization involved at least two distinct steps, a rapid uncoupling step, and a later loss of vasopressin receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence of two steps in the homologous desensitization of vasopressin-sensitive phospholipase C in WRK1 cells. Uncoupling and loss of vasopressin receptors. 296 82

Experiments were designed to study the effects of oxytocin on canine basilar and femoral arteries and to compare these with the effects of vasopressin. Rings of the arteries were suspended in physiological salt solution for isometric tension recording. Oxytocin and vasopressin caused endothelium-dependent relaxation of basilar arteries contracted with prostaglandin F2 alpha. Vasopressin was more potent than oxytocin. In the femoral artery, the two hormones caused endothelium-independent contractions with the same order of potency. The relaxations of the basilar artery occurred at lower concentrations of each substance than the contractions of the femoral artery. The relaxations in response to both agonists were inhibited competitively, and the contractions noncompetitively, by the V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP; the antagonist did not affect endothelium-dependent relaxations in response to bradykinin. Thus, both oxytocin and vasopressin cause endothelium-dependent relaxation of the basilar artery by activating V1-vasopressinergic receptors; the contractions of femoral arteries that they cause also may be mediated in part by V1-vasopressinergic receptors.
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PMID:Oxytocin causes endothelium-dependent relaxations of canine basilar arteries by activating V1-vasopressinergic receptors. 300 Dec 82

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

1. Pure non-peptide compounds obtained in crystal form from the crude extract of the plant Mandevilla velutina (Apocynaceae) were analysed for their antagonistic effects on rat uterine and guinea-pig smooth muscle contractions induced by bradykinin (Bk), lisyl-bradykinin (L-Bk), acetylcholine (ACh), oxytocin and histamine, in vitro. 2. Pre-incubation of rat uterine muscle with compounds MV 8608, MV 8609, MV 8610, MV 8611 and MV 8612 (5 to 40 micrograms ml-1) caused parallel and concentration-dependent rightward displacements of the Bk concentration-response curves (1 to 1000 nM). Schild plots of these data were linear (correlation close to 1) and yielded nominal pA2 values (g ml-1) of 5.7, 5.6, 5.4, 5.7 and 5.3, respectively. Compounds MV 8608, MV 8611 and MV 8612 (5 to 20 micrograms ml-1) also caused concentration-dependent and parallel displacements to the right of the concentration-response curve to L-Bk (1 to 10,000 nM). The Schild plots were linear and furnished nominal pA2 values (g ml-1) of 5.4, 5.8 and 5.1, respectively. With the exception of the antagonist effect of compound MV 8606 against Bk-induced contraction, all compounds behaved as simple competitive kinin antagonists since the calculated slopes were not different from unity. 3. In the guinea-pig ileum, both MV 8608 and MV 8612 (5 to 20 micrograms ml-1), produced concentration-dependent rightward displacements of the concentration-response curve to Bk (0.1 to 1000 nM) when the experiments were performed in the presence but not in the absence of atropine (2.5 microM). However, in contrast to the result obtained in the rat uterus, compound MV 8608 also caused a significant reduction of the maximal response to Bk. The Schild plot for compound MV 8612 was linear (correlation close to unity) and furnished a nominal pA2 value (g ml-1) of 5.3 and a slope not different from unity. 4. In rat uterine muscle, compounds MV 8608 and MV 8612 at concentrations producing marked rightward displacements of the kinin concentration-response curves (10 and 20 micrograms ml-1), did not influence the uterine contractile response to oxytocin or ACh, indicating some selectivity towards kinin receptors. Similarly, compound MV 8612 (10 and 20 ygml 1) did not interfere with the sensitivities or the maximal responses to ACh and histamine in the guinea-pig ileum, whereas compound MV 8608 (10 and 20ug ml-1) caused a slight reduction of ACh- and histamine-induced maximal contractions, allied to decrease of the sensitivity to histamine at concentrations of 20pgml-1 or more. 5. These results extend our previous data, indicating the existence of several non-peptide compounds in the crude extract of Mandevilla velutina that act as simple, competitive, selective and reversible kinin receptor antagonists in the rat isolated uterus and guinea-pig ileum smooth muscle.
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PMID:The competitive antagonistic effect of compounds from Mandevilla velutina on kinin-induced contractions of rat uterus and guinea-pig ileum in vitro. 320 77

Particulate fractions of human small intestinal mucosa contain an enzyme capable of hydrolyzing N-benzoyl-L-tyrosyl-p-aminobenzoic acid (PABA-peptide), a substrate used for clinical purposes to assess exocrine function of the pancreas (PABA test, pancreas function test). In this paper we describe the purification of PABA-peptide hydrolase (PPH) by immunoaffinity chromatography using a monoclonal antibody (Mab), HBB 3/716/36, bound to protein A-Sepharose, and the characterization of the purified enzyme. The final preparation of the enzyme was in the immobilized form, i.e., bound to Mab-protein A-Sepharose, and showed a 765-fold enrichment over the mucosal homogenate. The enrichment factor in purified microvillus membranes was comparable to that of sucrase-isomaltase, a microvillar marker enzyme. This, together with immunoelectron microscopy using protein A-gold, indicated that PPH is located in the apical membrane of intestinal epithelial cells. The enzyme was found to be present throughout the small intestine with the activity in distal ileum being 4.5-fold higher than that in the proximal duodenum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the immunoaffinity-purified PPH under reducing conditions revealed a polypeptide band with a relative molecular weight (Mr) of 100,000; under nonreducing conditions a major band with Mr 200,000 was observed. This indicates that PPH consists of two subunits with Mr 100,000 each, which are held together by one or more disulfide bonds. Two-dimensional polyacrylamide gel electrophoresis of the enzyme showed marked microheterogeneity, with pI's ranging from 6.0 to 6.85, probably due to glycosylation. The Km for PABA-peptide was 16.7 mM, and the pH optimum was 7.5-8.0 PPH activity was not inhibited by phenylmethylsulfonyl fluoride; pepstatin, leupeptin, amastatin, bestatin, puromycin, iodoacetate, or phosphoramidon. Activity was affected by captopril and Zinkov inhibitor, and in particular by thiol and chelating reagents. Chelator-inhibited PPH could be reactivated by bivalent metal ions, Zn2+ being the most effective. The enzyme catalyzed the hydrolysis of peptides including insulin B-chain, angiotensins I and II, bradykinin and bradykinin derivatives, oxytocin, and substance P, in each case yielding reproducible peptide fragments. On the basis of amino acid analysis of the products it could be concluded that peptides are hydrolyzed preferentially after an aromatic residue.
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PMID:N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase: a metalloendopeptidase of the human intestinal microvillus membrane which degrades biologically active peptides. 326 61

The effect of GnRH upon uterine contractions of both non-pregnant and pregnant rats was examined in vitro. In the non-pregnant rat uterus, GnRH inhibited in a concentration-and-time dependent manner the contractions induced by acetylcholine and oxytocin, but not those caused by bradykinin and angiotensin II. GnRH also inhibited the rhythmic contractions induced by oxytocin in uterine strips from late pregnant rats. These findings show that GnRH has a direct inhibitory effect on the rat uterine contractions, suggesting that GnRH-like substances may exert modulatory influences upon rat uterine contractility.
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PMID:Inhibitory effect of GnRH on isolated rat uterine muscle contractility. 329 Jun 5

The binding sites for [125I]LHRH were characterized in membranes from the hypthalamus and the effect of estrogen on the binding characteristics was studied in ovariectomized female rats. The radioligand, [125I]LHRH, was found to bind specifically to membranes from the hypothalamus at a maximal level, with an optimal temperature of 0 degrees C and a pH between 7 and 8. The binding was enhanced by NaCl at a concentration of 0.1-0.2 M. The specifically bound [125I]LHRH was only displaced by LHRH, but not by sodium iodide (NaI), bovine serum albumin and other hormones, such as thyrotropin-releasing hormone, bradykinin, oxytocin, prolactin, luteinizing hormone and growth hormone. The divalent metal ions, copper (Cu2+) and mercury (Hg2+), inhibited the specific binding of [125I]LHRH completely, whereas magnesium (Mg2+) and calcium (Ca2+) caused a decrease in binding. As revealed from Scatchard plot analysis, the binding sites for [125I]LHRH in the hypothalamus had a dissociation constant of 0.40 +/- 0.03 microM and the maximum number of binding sites was 98.55 +/- 4.34 pmol/mg protein. Treatment of female rates (ovariectomized for 3 weeks) with 4 micrograms of estradiol benzoate caused a statistically significant decrease in the maximal number of binding sites without any significant effect on the dissociation constant. However, the direct addition of estradiol hemisuccinate to the membrane preparations had no statistically significant effect on the specific binding of [125I]LHRH. The present study provides the evidence that estrogen decreases the density of binding sites for [125I]LHRH in the hypothalamus in vivo.
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PMID:The effect of estrogen on luteinizing hormone-releasing hormone binding sites in hypothalamic membranes. 331 92

Endothelial cells of the arterial wall can generate vasodilator and vasoconstrictor substances. The prototype of a vasodilator substance formed primarily in the endothelium is prostacyclin, although its main target under physiological conditions are the platelets. In addition, the endothelial cells respond to a variety of neurohumoral mediators by the liberation of an unidentified substance(s) (endothelium-derived relaxing factor) with a potent inhibitory effect on vascular smooth muscle, presumably because it accelerates the production of cyclic GMP in the latter. Endothelium-derived relaxing factor is very unstable, and has an extremely short half-life. It is inactivated by plasma proteins and thus does not fulfill a hormonal role. A metabolite of arachidonic acid may be involved in the production of endothelium-derived relaxing factor. Among the neurohumoral mediators which release it are: acetylcholine (through activation of muscarinic receptors), adenosine di- and triphosphate (P2-purinergic receptors), bradykinin, histamine (H1- or H2-histaminergic receptors, depending on the species), serotonin (S1-serotonergic receptors), substance P, oxytocin, thrombin and vasopressin (V1-vasopressinergic receptors). The release of the factor can also be triggered by aggregating platelets (because they release adenine nucleotides and serotonin) and by increases in shear stress. It is likely that endothelium-dependent dilatation helps to prevent intraluminal coagulation in arteries with a normal intima. Absence, or dysfunction of the endothelium may favor the occurrence of vasospasm. Endothelium-dependent relaxations are reduced in atherosclerotic blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The endothelium and arterial reactivity]. 349 May 30

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

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
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PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8


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