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)

The involvement of serotonin (5-HT) in oxytocin secretion was investigated in this study. Pharmacologic agents that influence serotonergic transmission were administered to conscious unrestrained male rats 30 min prior to sacrifice and plasma oxytocin concentration was measured by radioimmunoassay. The d- and l-stereoisomers of the 5-HT releaser fenfluramine significantly increased plasma oxytocin in a dose-dependent manner. Oxytocin secretion was more potently stimulated by d-fenfluramine than by l-fenfluramine. The 5-HT releaser p-chloroamphetamine also increased plasma oxytocin. The following 5-HT agonists increased plasma oxytocin concentration: the 5-HT1&2 agonist m-chlorophenyl-piperazine [10-20 mg/kg intraperitoneally (i.p.)], the 5-HT1C&2 agonist 1-(2,5-dimethoxy-4-l-phenyl)-2-aminopropane (0.5-2.0 mg/kg i.p.) and the 5-HT1&2 agonist 1-piperazinyl-6-chloropyrazine (10 mg/kg i.p.). In contrast, the 5-HT1AB agonist 5-methoxy-3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole (0.2-5.0 mg/kg i.p.) did not increase oxytocin secretion. Pretreatment with the 5-HT1C&2 antagonist, 6-(2-(4-[bis(4-fluorophenyl)methylene]-1-piperidinyl)ethyl)-7-methyl-5H- thiazolo(3(1)2-a)pyrimidin-5-one [2.5 mg/kg subcutaneously (s.c.)], 60 min before injection of 1-piperazinyl-6-chloropyrazine attenuated, but did not completely block, 1-piperazinyl-6-chloropyrazine-induced secretion of oxytocin. Both low and high (0.01 and 0.1 mg/kg s.c.) doses of 6-(2-(4-[bis(4-fluorophenyl)methylene]-1-piperidinyl)ethyl)-7-methyl-5H- thiazolo(3(1)2-a)pyrimidin-5-one or the 5-HT2 antagonist spiperone inhibited the 1-(2,5-dimethoxy-4-l-phenyl)-2-aminopropane-induced increases in plasma oxytocin. These studies provide evidence that enhanced serotonergic transmission stimulates oxytocin secretion and that 5-HT2 receptors contribute to this effect.
 ...
PMID:Enhanced serotonergic transmission stimulates oxytocin secretion in conscious male rats. 185 Apr 81

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.
 ...
PMID:Bradykinin agonist activity of a novel, potent oxytocin antagonist. 189 11

At 500 micrograms-4 mg/ml piperazine and the anti-Ascaris fraction of the ethanolic extract of the bark of the erin tree (Polyadoa umbelleta) have equipotent inhibitory effects on submaximal contractions induced by equipotent doses of acetylcholine, nicotine and 5-hydroxytryptamine on the guinea-pig ileum and the rabbit duodenum. Similar inhibitory effects were noted on: acetylcholine, adrenaline, histamine, and barium chloride-induced contractions in the guinea-pig vas deferens, oxytocin and acetylcholine-induced contractions in the non-pregnant rat uterus. These actions indicate that piperazine and erin possess definite non-specific smooth muscle depressant properties. The need for the elucidation of the chemical nature of the active constituent in "erin" and for in-vivo anti-Ascaris activity studies in man is stressed.
 ...
PMID:Effects of piperazine citrate and of the anti-Ascaris fraction of the ethanolic extract of the bark of Polyadoa umbellata (erin) on mammalian non-vascular smooth muscle. 647 82

1-(3-Chlorophenyl)piperazine (m-CPP) (0.1-4 mg/kg s.c.) and N-(3-trifluoromethylphenyl)-piperazine (TFMPP) (0.5-4 mg/kg s.c.), 5-HT1C receptor agonists, but not 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) (0.1 and 0.2 mg/kg s.c.), a 5-HT1A receptor agonist, induced penile erection and yawning with a U-inverted dose-response curve in male rats. The maximal effect was found with 0.5 mg/kg s.c. of m-CPP and with 1 mg/kg s.c. of TFMPP. The m-CPP (0.5 mg/kg s.c.) and TFMPP (1 mg/kg s.c.) responses were prevented by mianserin (0.2 mg/kg s.c.) and by ritanserin (1 mg/kg s.c.) given 15 min before m-CPP and TFMPP. In contrast, m-CPP- or TFMPP-induced penile erection and yawning were not antagonized by haloperidol (0.1 mg/kg s.c.) or by [d(CH2)5Tyr(Me)2,Orn8]vasotocin (5 micrograms i.c.v.). Apomorphine- and oxytocin-induced penile erection, but not yawning, was also antagonized by mianserin and less effectively by ritanserin. The results suggest that 5-HT1C receptor agonist-induced penile erection and yawning are not mediated by increased dopaminergic and/or oxytocinergic transmission, and raise the possibility that a neuronal dopamine-oxytocin-5-HT link is involved in the control of penile erection and not necessarily of yawning in male rats.
 ...
PMID:Penile erection and yawning induced by 5-HT1C receptor agonists in male rats: relationship with dopaminergic and oxytocinergic transmission. 800 37

The present experiments were designed to investigate the mechanisms involved in the contractile responses evoked by KCl, added either isoosmotically or hyperosmotically, in the rat uterus. Exposure of uterine strips to a Ca(2+)-free, 3 mM EGTA-containing solution abolished the responses induced by isoosmotic KCl solutions. Conversely, addition of hyperosmolar KCl induced concentration-dependent tonic responses in a Ca(2+)-free, 3 mM EGTA-containing solution. The maximum increase in tension was reached with 210 mM K+. The response to hyperosmotic K+ was unaffected by previous depletion of intracellular Ca2+ stores with oxytocin (1 microM), by inhibition of refilling of the intracellular Ca2+ stores using cyclopiazonic acid (10 microM) or by increasing the concentration of EGTA in the medium to 10 mM. Sucrose and mannitol (60-420 mM) induced concentration-dependent sustained contractions which were not reproducible and were significantly smaller in size than those evoked by the maximally effective concentration of hyperosmotic K+ (210 mM). The contraction induced by hyperosmotic K+ in Ca(2+)-free solution was not altered by the calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7, 100 microM), the Ca2+/calmodulin protein kinase II inhibitor 1-[N,O-bis(1,5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine (KN-62, 10 microM) or the tyrosine kinase inhibitor genistein (10 microM). The protein kinase C inhibitor calphostin C (1-3 microM) failed to modify the K(+)-effect curve, which was however partially inhibited in the presence of the non-selective protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2 methylpiperazine dihydrochloride (H-7, 3-100 microM). The protein kinase inhibitor staurosporine (30-300 nM) depressed the contraction induced by hyperosmolar K+ in a concentration-dependent manner. The contraction induced by sucrose in Ca(2+)-free solution was unaffected by W-7 (100 microM) and KN-62 (10 microM) but was partially reduced by calphostin C (1 microM), H-7 (30 microM), staurosporine (100 nM) and genistein (10 microM). These results suggest that different mechanisms are involved in the responses evoked by isoosmotic and hyperosmotic KCl in the rat uterus. A component of the contraction induced by hypertonic KCl seems mainly independent of both external and internal Ca2+ and of hyperosmolar stress. This contraction is not mediated by protein kinase C, Ca2+/calmodulin-dependent kinases or protein tyrosine kinases but involves activation of other, at the present unknown, staurosporine-sensitive protein kinase(s).
 ...
PMID:Ca(2+)-independent contraction induced by hyperosmolar K(+)-rich solutions in rat uterus. 889 13