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)

JTP-4819 ((S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N- phenylmethyl)-1-pyrrolidinecarboxamide) is a potent (IC50: 0.83 +/- 0.09 nM in rat brain supernatant; 5.43 +/- 0.81 nM in Flavobacterium meningosepticum) and specific inhibitor of prolyl endopeptidase (PEP). JTP-4819 (3 mg/kg p.o.) exhibited a strong and durable ex vivo inhibitory effect on PEP in various regions of the rat brain. In addition, JTP-4819 inhibited the degradation of substance P, arginine-vasopressin, thyrotropin-releasing hormone, neurotensin, oxytocin, bradykinin, and angiotensin II by purified PEP with IC50 values of 9.6, 13.9, 10.7, 14.0, 4.5, 7.6 and 10.6 nM, respectively. In the one-trial passive avoidance test in rats with scopolamine-induced amnesia, JTP-4819 significantly prolonged the retention time when administered orally at doses of 1 and 3 mg/kg 1 hr before acquisition or at 3 and 10 mg/kg 1 hr before retention. In addition, coadministration of JTP-4819 and substance P, arginine-vasopressin or thyrotropin-releasing hormone (at doses at which each drug alone did not prolong the retention time) improved the retention time of rats with scopolamine-induced amnesia. Microdialysis studies demonstrated that JTP-4819 caused a significant increase in ACh release in the frontal cortex and hippocampus of young rats at oral doses of 1 and 3 mg/kg, as well as in both brain regions of aged rats at a dose of 3 mg/kg. These results indicate that JTP-4819 potentiates neuropeptide functions inhibiting PEP, that it activates cholinergic transmission and that it enhances learning and memory.
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PMID:JTP-4819: a novel prolyl endopeptidase inhibitor with potential as a cognitive enhancer. 756 10

Effect of extracellularly applied oxytocin was investigated on snail neurons in cell attached single channel recording configuration. OXT activated Cl-dependent inward and outward current with amplitude of 1.4 and 1.6 pA, respectively. OXT have affected the ACh-activated current decreasing or increasing the mean interburst interval of single channel activity.
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PMID:Patch-clamp studies of the oxytocin-induced effects in Helix pomatia L. neurons. 768 76

Motility of Fallopian tubes is essential for transport of ova from peritoneal cavity uterus. Numerous substances were found to affect motility of the tubes. Catecholamines cause both relaxation and contraction isolated Fallopian tubes; it depends on type of receptor they bind for. Acetylcholine, neurotensin and oxytocin stimulate motility of the tubes, while gamma-aminobutyric acid, vasoactive intestinal peptide and substance P have an inhibitory role. Numerous cytokines and their receptors were found in human oviducts; their effects on motility remain to be established. The whole sequence of events in regulation of oviducts motility is still unknown so further investigation in the field is required.
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PMID:[Neurohumoral regulation of Fallopian tube motility]. 864 53

Stageness in the protein glands development is influenced by the nervous system mediators. Adrenergic mediation was established not to be developed by the period of provisory differentiation and appears to grow weaker by senile age. Acetylcholine stimulates growth and proliferation in the form of layers and bands. Adrenalin exerts its influence on organotypical level, which manifestates in reservation of the specific differentiation and protein type functioning of the gland. Hypothalamic neurohormones (oxytocin, vasopressin) influence the maintainance of the secretory epithelium viability.
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PMID:[The morphofunctional characteristics of the epithelium of the salivary glands and the neuroendocrine regulation of its histogenesis]. 868 39

1. Arginine-vasopressin (VP) has both vasoconstricting and vasodilating action. We report here the discovery of four novel selective hypotensive VP analogues: d(CH2)5[D-Tyr(Et)2,Arg3,Val4]AVP; d(CH2)5[D-Tyr(Et)2,Lys3,Val4]AVP and their iodinatable Tyr-NH2(9) analogues. 2. Bioassays in rats for activities characteristic of neurohypophysial peptides showed that the four VP peptides possessed little or no V1a, V2 or oxytocin (OT) receptor agonistic or antagonistic activities. 3. In anaesthetized rats, these peptides (0.05-0.10 mg kg(-1) i.v.) elicited a marked fall in arterial blood pressure. 4. Blockade of cholinoceptors, adrenoceptors and bradykinin B2 receptors, and inhibition of prostaglandin synthesis had little effect on their vasodepressor action. 5. Classical V1a, V2 and OT receptor antagonists did not block the vasodepressor response. 6. L-NAME, 0.2 mg kg(-1) min(-1), markedly suppressed the hypotensive response to ACh but not the vasodepressor response to the hypotensive VP peptides. However, the duration of the vasodepressor response was shortened. Very high doses of L-NAME attenuated both the vasodepressor response and the duration of action. 7. These findings indicate that the vasodepressor action of these VP peptides is independent of the peripheral autonomic, bradykinin and PG systems and is not mediated by the known classical OT/VP receptors. NO does not appear to have an important role in their vasodepressor action. 8. The discovery of these novel VP peptides could lead to the development of new tools for the investigation of the complex cardiovascular actions of VP and the introduction of a new class of hypotensive agents. The two iodinatable hypotensive VP peptides could be radiolabelled as potential markers for the localization of the receptor system involved.
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PMID:Discovery of novel selective hypotensive vasopressin peptides that exhibit little or no functional interactions with known oxytocin/vasopressin receptors. 983 18

The influence of N -ethyl- and N -benzyl-1,2-diphenyl ethanolamines (compounds E and B, respectively) was examined on the spontaneously contracting rabbit jejunum and the rat uterus together with their influence on the contractions induced by some spasmogens in the guinea-pig ileum and oxytocics and CaCl2in the pregnant rat uterus. Both E and B inhibited the spontaneous contractions of the rabbit jejunum with ID50values of 0.13 and 0.03 micromol ml-1. Their inhibitory activities were not antagonized by alpha- or beta-adrenoceptor blockers but significantly reversed by CaCl2(0.015 micromol ml-1). The compounds also antagonized nicotine, ACh-, histamine-, 5-HT- and CaCl2-induced contractions by 44-100%. Compound E seemed to be several times more potent than B in inhibiting the spontaneous uterine contractions with an ID50of (7 nmol ml-1). Their inhibitory effects were not antagonized by beta2-adrenoceptor or H2-receptor blocking drugs. Both compounds (40 nmol ml-1) antagonized in a competitive manner CaCl2-induced contractions in the K+-depolarised uterus and PGE2and oxytocin-induced uterine contractions. The ID50values were in the range of 1.6-10.7 nmol ml-1. The results suggest that E and B compounds may be considered as putative L-Ca2+channel blockers with certain selectivities. The E compound seemed to be more selective against uterine L-Ca2+channels and the B compound against intestinal smooth muscles. Thus, the compounds may be of potential value in treatment of some colics, the irritant bowel syndrome, dysmenorrhoea and premature deliveries.
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PMID:Studies on the spasmolytic and uterine relaxant actions of n -ethyl and n -benzyl-1,2-diphenyl ethanolamines: elucidation of the mechanisms of action. 1037 39

The effects of the antivenene fraction of an ethanol extract of Diodia scandens on some mammalian smooth muscles were investigated. On the guinea-pig ileum, the extract was shown to be a partial agonist acting via muscarinic receptors. Acetylcholine (ACh) was 2.5 x 10(5) times more potent. On the pregnant guinea-pig uterus, the extract induced concentration-dependent increases in the force of contraction and tonus. Oxytocin and ergometrine were respectively 10(6) and 10(3) times more potent. The extract, at subliminal concentrations, potentiated ACh and adrenaline-induced contractions in the guinea-pig was deferens. It also induced dose-related vasodilatation in the rat hindquarters and depressed the blood pressure in the anaesthetized cat. It was concluded that these pharmacological actions offer some scientific explanation for the use of Diodia scandens in traditional medicine as a laxative and as an oxytocic agent. It is suggested that the extract could enhance erection and ejaculatory processes in the male, thus accounting for its regular use by some elderly males.
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PMID:Pharmacological basis for the use of the antivenene water soluble extract of Diodia scandens as a laxative, oxytocic agent and a possible aphrodisiac in traditional medicine practice in eastern Nigeria. 1047 53

The aim of the present study was to clarify the cellular mechanisms underlying the alpha(2)-adrenoceptor-mediated contraction of porcine myometrium (nonvascular smooth muscle). Acetylcholine (3 nM-1 microM), clonidine (1 nM-10 microM) and 5-bromo-N-[2-imidazolin-2-yl]-6-quinoxalinamine (UK14304) (1 nM-10 microM) in Krebs solution caused a concentration-dependent contraction in the longitudinal muscles of the porcine uterus with similar EC(50) values and maximum responses. A lowered external Ca(2+) concentration and verapamil (10 nM-10 microM) decreased the contractile response to clonidine and UK14304 more markedly than the response to acetylcholine. However, in Kumagai solution, neither clonidine nor UK14304 caused contractile responses, but acetylcholine remained effective. The effects of alpha(2)-adrenoceptor agonists on intracellular Ca(2+) concentration ([Ca(2+)](i)) and smooth muscle force were measured simultaneously using fura-PE3-loaded muscle preparations. Clonidine and UK14304 caused increases in [Ca(2+)](i) and force of the longitudinal muscle. The increases in [Ca(2+)](i) and muscle force were markedly inhibited by verapamil and in Ca(2+)-free solution (EGTA, 1 mM). In the absence of external Ca(2+), clonidine caused only a small increase in [Ca(2+)](i) in Ca(2+)-loaded preparations compared with those increases caused by carbachol, histamine, and oxytocin. Ca(2+) (2.5 mM) caused increases in [Ca(2+)](i) and force of the longitudinal muscles in a Ca(2+)-free high K(+) solution. Clonidine concentration dependently potentiated the Ca(2+)-induced contraction without significantly changing the increase in [Ca(2+)](i), and this potentiation was inhibited by yohimbine. These results suggested that clonidine increases the Ca(2+) sensitivity of the contractile elements through activation of alpha(2)-adrenoceptors. During the development of the contractile response to clonidine (1 microM, 0-5 min), tissue cyclic AMP levels did not change significantly. In vitro treatment with pertussis toxin (1 microg/ml for 2 h) significantly decreased the contraction induced by clonidine without affecting the responses to carbachol and high K(+). The present results indicate that in porcine myometrium, alpha(2)-adrenoceptor stimulation caused contraction of the longitudinal muscles by mechanisms largely dependent on the influx of extracellular Ca(2+), probably through voltage-dependent Ca(2+) channels (VDCCs), and that the potentiation of the Ca(2+) sensitivity of the contractile elements is another mechanism of the contractile responses. These actions involve a pertussis-toxin-sensitive G protein (probably G(i) type) in the signal transduction pathway.
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PMID:The mechanisms of alpha(2)-adrenoceptor agonist-induced contraction in longitudinal muscle of the porcine uterus. 1070 23

The effects of close intra-arterial infusion of acetylcholine and adrenalin on ovarian secretion of progesterone and oxytocin were examined on Day 10 of the estrous cycle in goats (estrus = Day 0). Acetylcholine (15 micrograms/min) was without effect, but adrenalin (10 micrograms/min) significantly (P < 0.001) raised both progesterone and oxytocin concentrations in ovarian vein plasma. These results show that luteal hormone secretion is enhanced in the goat by beta-adrenergic stimulation and suggest that, as in the sheep and cow, there may be neuroendocrine involvement in the regulation of caprine luteal function.
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PMID:Effects of arterial infusions of adrenalin and acetylcholine on luteal secretion of progesterone and oxytocin in goats. 1073 92

The effects of both Dai-kenchu-to and PGF(2alpha) on intestinal and uterine motility were studied in anaesthetized rabbits with force transducers implanted in the jejunum, ileum and uterus. A single intraduodenal administration of Dai-kenchu-to (300 mg/kg) enhanced the intestinal motility but not the uterine motility. However, intravenous administration of PGF(2alpha) (20 microg/kg) enhanced both intestinal and uterine motility. The effects of Dai-kenchu-to on the spontaneous contraction and contractile response of the isolated rat uterine strips to oxytocin, PGF(2alpha) or ACh were also studied. Oral administration of Dai-kenchu-to at 300 mg/kg for one week had no effect on either the spontaneous contraction or the contractile response of the uterus. These results indicate that Dai-kenchu-to may exert stimulatory effects on intestinal motility, as PGF(2alpha), but has no effect on the uterine motility, suggesting a selective effect on the gastrointestinal tract. Hence, Dai-kenchu-to may be safer than PGF(2alpha) in the treatment of postoperative adhesive ileus in women. However, more studies are needed to determine whether Dai-kenchu-to could be administered to pregnant women.
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PMID:Effects of Dai-kenchu-to, a herbal medicine, on uterine and intestinal motility. 1140 52


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