Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of hexarelin and four related peptide analogues, EP 40904, EP 40737, EP 50885 and EP 60761, injected into the paraventricular nucleus of the hypothalamus of male rats in doses between 2 and 2000 ng on spontaneous penile erection was studied. Of these peptides, EP 60761 and EP 50885, but not hexarelin, EP 40904 or EP 40737, increased dose-dependently the number of spontaneous penile erections. EP 60761 was active already at the dose of 20 ng, which induced the sexual response in 70% of the treated rats. The maximal response was induced by 200 ng of the peptide. EP 50885 was less potent than EP 60761, with 1000 ng being the minimal effective dose and 2000 ng as the dose required to induce the maximal response. At the doses used, both peptides also increased slightly the number of spontaneous yawning episodes. EP 60761- and EP 50885-induced penile erection was prevented by the oxytocin receptor antagonist [d(CH(2))(5)Tyr(Me)(2)-Orn(8)]vasotocin (0.1-1 microg) given intracerebroventricularly (i.c.v.), but not into the paraventricular nucleus (0.1-1 microg), by the competitive nitric oxide (NO) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) given either into the paraventricular nucleus (10-20 microg) or i.c.v. (75-150 microg), by the N-type Ca(2+) channel blocker omega-conotoxin-GVIA (2-5 ng) or by the opiate morphine (1-10 microg), but not by the dopamine receptor antagonist (Z)-4-[3-[2-(trifluoromethyl)-9H-thioxanthen-9-ylidene]propyl]-1-p ipe razine-ethanol (cis-flupenthixol) (10 microg) or by the N-methyl-D-aspartic acid (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine ((+)-MK-801) (1 microg), all given into the paraventricular nucleus before either peptide. The present results show that EP 60761 and EP 50885 induced penile erection by increasing central oxytocin transmission, possibly by activating NO synthase in the cell bodies of oxytocinergic neurons located in the paraventricular nucleus that control penile erection.
 ...
PMID:EP 60761 and EP 50885, two hexarelin analogues, induce penile erection in rats. 1098 Feb 72

We have previously shown that oxytocin receptors are present in the heart and that perfusion of isolated rat hearts with oxytocin results in decreased cardiac flow rate and bradycardia. The mechanisms involved in the negative inotropic and chronotropic effects of oxytocin were investigated in isolated dog right atria in the absence of central mechanisms. Perfusion of atria through the sinus node artery with 10(-6) mol/L oxytocin over 5 minutes (8 mL/min) significantly decreased both beating rate (-14.7+/-4.9% of basal levels, n=5, P<0.004) and force of contraction (-52.4+/-9.1% of basal levels, n=5, P<0.001). Co-perfusion with 10(-6) mol/L oxytocin receptor antagonist (n=3) completely inhibited the effects of oxytocin on frequency (P<0.04) and force of contraction (P<0.004), indicating receptor specificity. The effects of oxytocin were also totally inhibited by co-perfusion with 5x10(-8) mol/L tetrodotoxin (P<0.02) or 10(-6) mol/L atropine (P<0.03) but not by 10(-6) mol/L hexamethonium, which implies that these effects are neurally mediated, primarily by intrinsic parasympathetic postganglionic neurons. Co-perfusion with 10(-6) mol/L NO synthase inhibitor (L-NAME) significantly inhibited oxytocin effects on both beating rate (-1.85+/-1.27% versus -14.7+/-4.9% in oxytocin alone, P<0.05) and force of contraction (-24.9+/-4.4% versus -52.4+/-9.1% in oxytocin alone, n=4, P<0.04). The effect of oxytocin on contractility was further inhibited by L-NAME at 10(-4) mol/L (-8.1+/-1.8%, P<0.01). These studies imply that the negative inotropic and chronotropic effects of oxytocin are mediated by cardiac oxytocin receptors and that intrinsic cardiac cholinergic neurons and NO are involved in these actions.
 ...
PMID:Negative inotropic and chronotropic effects of oxytocin. 1150 92

The effect of cannabinoid CB1 receptor agonists and antagonists on penile erection was studied in male rats when injected into the paraventricular nucleus of the hypothalamus. The CB1 receptor antagonist SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide] (0.5-5 microg) induced penile erection in a dose-dependent manner. The minimal effective dose was 1 microg, while the maximal response was found with 5 microg of the compound. In contrast, the CB1 receptor agonists WIN 55,212-2 [4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1-I,j]quinolin-6-one] (0.5-5 microg) and CP 55,940 [1alpha,2beta-(R)-5alpha]-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxy-propyl)cyclohexyl]phenol (0.5-5 microg) were ineffective at all the doses tested. Nevertheless, both compounds reduced the enhancing effect of SR 141716A on penile erection when given into the paraventricular nucleus at the above doses before SR 141716A. The pro-erectile effect of SR 141716A was also reduced by the non-competitive NMDA receptor antagonist dizolcipine (MK-801) (0.2 microg) and by the NO synthase inhibitor NG-nitro-l-arginine methylester (L-NAME) (20 microg) but not by the dopamine receptor antagonist cis-flupenthixol (10 microg) or the oxytocin receptor antagonist d(CH2)5Tyr(Me)2-Orn8-vasotocin (0.1 microg), when given into the paraventricular nucleus. In spite of its inability to prevent the pro-erectile effect of SR 141716A when given in the paraventricular nucleus, d(CH2)5Tyr(Me)2-Orn8-vasotocin) (1 microg) reduced almost completely SR 141716A-induced penile erection when given into the lateral ventricles. The present results show that cannabinoid CB1 receptors present in the paraventricular nucleus may influence erectile function and sexual activity by modulating paraventricular oxytocinergic neurons mediating erectile function.
 ...
PMID:Antagonism of cannabinoid CB1 receptors in the paraventricular nucleus of male rats induces penile erection. 1505 Jul 1

The effect of four peptides derived from the C-terminal portion of rat pro-VGF(556-617) (VGF(556-576), VGF(588-617), VGF(599-617), and VGF(588-597)), on penile erection and nitric oxide production in the paraventricular nucleus of the hypothalamus was studied in male rats after injecting into this hypothalamic nucleus. VGF(588-617) (0.5, 1 and 2 microg), VGF(599-617) (0.5, 2 and 5 microg) and, to a lower extent, VGF(588-597) (2 and 5 microg) induced penile erection episodes when injected into the paraventricular nucleus and concomitantly increased paraventricular nitric oxide production, while VGF(556-576) (5 microg) was ineffective. VGF(588-617)-induced nitric oxide production was reduced by N(G)-nitro-l-arginine methylester (l-NAME) (20 microg), a nitric oxide synthase inhibitor, which also reduced penile erection when injected in the paraventricular nucleus 15 min before the VGF peptide. The oxytocin receptor antagonist d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin (1 microg) also effectively reduced VGF(588-617)-induced penile erection when given into the lateral ventricles, but not when injected into the paraventricular nucleus. In both experimental conditions, d(CH(2))(5)Tyr(Me)-Orn(8)-vasotocin was unable to influence nitric oxide production in the paraventricular nucleus. The present results confirm that C-terminal pro-VGF-derived peptides induce penile erection when injected into the paraventricular nucleus and show that this effect is mediated by an increased nitric oxide production in this hypothalamic nucleus. Apparently, this causes the activation of paraventricular oxytocinergic neurons projecting to extra-hypothalamic brain areas and mediating penile erection, as found with dopamine agonists, oxytocin, excitatory amino acids and hexarelin analogue peptides.
 ...
PMID:Pro-VGF-derived peptides induce penile erection in male rats: Involvement of paraventricular nitric oxide. 1608 1

Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs).
 ...
PMID:Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins. 2654 94