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)

1. Recent experimental evidence has shown that nitric oxide (NO) plays an important role in the expression of penile erection and yawning and that this molecule has to be added to the list of the best known neurotransmitters and neuropeptides involved in this symptomatology. 2. This was first suggested by the ability of NO synthase inhibitors injected in the lateral ventricles (i.c.v.) or in the paraventricular nucleus of the hypothalamus (PVN) to prevent these behavioral responses induced by dopamine agonists, oxytocin and NMDA. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were injected concomitantly with L-arginine, the precursor of NO. Most important, this hypothalamic nucleus is one of the richest brain areas of NO synthase and also the brain site where dopamine, NMDA and oxytocin act to induce penile erection and yawning by activating central NO synthase containing oxytocinergic neurons. 3. NO synthase inhibitors given i.c.v. but not in the PVN prevent also penile erection and yawning induced by ACTH and serotonin1c agonists, which induce these responses by acting with mechanisms unrelated to oxytocinergic transmission. 4. Dopamine agonists, NMDA and oxytocin increase NO production in the PVN at doses that induce penile erection and yawning, as determined by measuring the concentration of NO2- and NO3- in the dialyzate obtained with a vertical probe implanted in the PVN by in vivo microdialysis. 5. NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce penile erection and yawning indistinguishable from those induced by oxytocin, dopamine agonists or NMDA when injected in the PVN. The NO donor response was prevented by the i.c.v. injection of the oxytocin receptor antagonist d(CH2)5-Tyr(Me)-Orn8-vasotocin, indicating that these compounds also induce penile erection and yawning by activating oxytocinergic transmission. 6. Finally, guanylate cyclase inhibitors (i.e. methylene blue and LY 83583) and hemoglobin injected in the PVN do not prevent drug-induced penile erection and yawning, nor 8-Br-cGMP injected in the PVN induces these behavioral responses suggesting that the mechanism by means of which endogenous or NO donor-derived NO facilitates oxytocinergic transmission to induce penile erection and yawning is not related to the activation of guanylate cyclase. Furthermore, since hemoglobin, in spite of its ability to prevent drug-induced NO production in the PVN, does not prevent penile erection and yawning, it is likely that NO acts as an intracellular rather than an intercellular modulator in the PVN neurons in which is formed to facilitate the expression of these behavioral responses.
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PMID:Role of central nitric oxide in the control of penile erection and yawning. 938 Jul 88

Yawning is a phylogenetically old, stereotyped event that occurs alone or associated with stretching and/or penile erection in humans, in animals from reptiles to birds and mammals, under different conditions. Several neurotransmitters and neuropeptides are involved in its control at the central level. One of these at the level of the paraventricular hypothalamic nucleus (PVHN) is nitric oxide (NO). First, NO synthase inhibitors injected into this hypothalamic nucleus prevent yawning induced by dopamine agonists, oxytocin or N-methyl-D-aspartic acid (NMDA), which induce yawning by activating PVHN oxytocinergic neurons projecting to extra-hypothalamic brain areas. The inhibitory effect of NO synthase inhibitors was not observed when these compounds were given concomitantly with L-arginine, the precursor of NO. Second, dopamine agonists, NMDA and oxytocin given at doses that induce yawning, increase NO production in the PVHN, as determined by in vivo microdialysis. Conversely, the opiate morphine, which prevents yawning induced by dopamine agonists, oxytocin and NMDA, also prevents the increase in the paraventricular NO production induced by these compounds. Third, NO donors, such as nitroglycerin, sodium nitroprusside and hydroxylamine, induce yawning when injected into the PVHN apparently by activating oxytocinergic transmission. Since guanylate cyclase inhibitors and NO scavengers (hemoglobin) injected into the PVHN do not prevent drug-induced yawning, nor 8-Br-cGMP injected into the PVHN induces this behavioral response, it is likely that NO acts as an intracellular rather than an intercellular modulator inside the PVHN oxytocinergic neurons in which NO is formed to facilitate the expression of this phylogenetically old event by guanylate cyclase-independent mechanisms.
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PMID:Yawning: role of hypothalamic paraventricular nitric oxide. 1124 84

We tested both relaxation and cGMP generation by atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) in oxytocin-stimulated myometrium from near-term pregnant guinea pigs to investigate the ability and mechanism of natriuretic peptides to inhibit myometrial contractility. Myometrial strips were contracted by 10(-8) M oxytocin, and relaxation to the cumulative addition (10(-9)-10(-6) M) of the natriuretic peptides measured. Maximal relaxation to BNP was significantly greater than to ANP (52 versus 32% respectively; p < 0.05), whereas CNP failed to produce relaxation. However, the increase in cGMP produced by BNP (10(-7) M) was significantly less than that produced by ANP (10(-7) M) (4.5 versus 7.0 times basal; p < 0.05); CNP did not increase myometrial cGMP. Anantin, a competitive blocker of the guanylate cyclase A receptor, significantly reduced the increase in cGMP produced by ANP and BNP, but had no effect on relaxation induced by either peptide. Rp-8-Br-cGMP, an inhibitor of the cGMP-dependent protein kinase, did not alter BNP-induced relaxation. The atrial natriuretic peptide-fragment 4-23 amide, a natriuretic peptide clearance receptor agonist, failed to inhibit oxytocin-stimulated myometrial contraction. We conclude that natriuretic peptide induced relaxation of oxytocin-stimulated myometrium from the pregnant guinea pig is not mediated by either guanylate cyclase A or B activation, is independent of the cGMP pathway, and does not involve clearance receptor activation. Our results suggest that natriuretic peptide-induced relaxation of pregnant myometrium is mediated via a novel mechanism.
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PMID:Natriuretic peptide-induced relaxation of myometrium from the pregnant guinea pig is not mediated by guanylate cyclase activation. 1125 43

Our objective was to test the hypothesis that the cGMP signal-transduction mechanism mediates nitric oxide's (NO) modulation of oxytocin (OT) and vasopressin (VP) secretion from the hypothalamo-neurohypophysial system. Three studies were conducted in adult male Sprague-Dawley rats: (1a) Euhydrated rats received an intracerebroventricular (icv) infusion (1 microl/min for 30 min) of artificial cerebrospinal fluid (aCSF), vehicle (2.6% dimethyl sulfoxide [DMSO]) or 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (0.05 microg/microl), an inhibitor of soluble guanylyl cyclase (sGC). ODQ did not affect basal levels of plasma VP or OT; (1b) Rats dehydrated for 24 h received aCSF or 8-Br-cGMP (icv), a membrane-permeable analog of cGMP, and plasma hormones were measured 2 min later. 8-Br-cGMP did not significantly change VP or OT levels; (2) Rats ingested water or 2% NaCl for 4 days, and NO synthase (NOS) and sGC activities were measured in posterior pituitaries, the anatomical site of hormone secretion. Salt loading enhanced (P < 0.001) production of [(14)C]citrulline, the coproduct of NO synthesis, without altering cGMP; (3) One SON was microdialyzed with [(14)C]arginine and NOS and sGC activities were quantified in microdialysates during intravenous (iv) infusion of isotonic or hypertonic saline in awake and anesthetized rats. In awake rats, [(14)C]citrulline recovery, but not cGMP, increased (P < 0.05) during intravenous infusion of both isotonic and hypertonic solutions, and after insertion of microdialysis probe itself. In anesthetized rats, however, where basal NOS activity is low, intravenous infusion of hypertonic, but not isotonic solution, increased [(14)C]citrulline recovery without affecting cGMP. Thus, in the forebrain, neither NO produced basally nor during osmotic stimulation depends on cGMP to modulate plasma vasopressin and oxytocin secretion.
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PMID:NO inhibition of the magnocellular neuroendocrine system in rats is independent of cGMP signaling pathway. 1476 77

Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down- and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by i.c.v. 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.
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PMID:Nitric oxide modulation of the hypothalamo-neurohypophyseal system. 1506 7