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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of phosphodiesterase inhibitors, an activator and an inhibitor of guanylyl cyclase, and cAMP and cGMP analogs on oxytocin-induced contractions have been studied in the testicular capsule of rats. The nonspecific phosphodiesterase inhibitors, theophylline and caffeine, attenuated the oxytocin-induced contractions via mechanisms that seem to be related to an increase in cAMP levels, since a similar effect was produced by dibutyryl cAMP. Sodium nitroprusside facilitated oxytocin-induced contractions. This effect was mimicked by dibutyryl cGMP. Methylene blue, an inhibitor of soluble guanylyl cyclase, decreased oxytocin-induced contractions, which suggests an involvement of guanylyl cyclase in the oxytocin effect. These results suggest that cAMP modulates the contraction and that cGMP, contrary to what happens in most smooth muscles, could participate in oxytocin-induced contractions in the testicular capsule of rats.
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PMID:Role of cyclic nucleotides in contraction induced by oxytocin in the testicular capsule of the rat in vitro. 899 Apr 88

This paper discusses the current evidence supporting the notion that endogenous carbon monoxide (CO) is a modulator of neuroendocrine function. CO is normally formed in the body during the enzymatic catabolism of heme moieties by heme oxygenase (HO). Three HO isoforms have been described to date: HO-1, HO-2 and HO-3. In the brain, CO is principally generated by HO-2 but, in discrete brain areas such as the paraventricular nuclei of the hypothalamus, a role for HO-1 is also possible. Moreover, under pathological conditions, the latter isoform is expressed by activated glial cells. The possible contribution by the recently described HO-3 remains to be established. Once formed, CO exerts its biological effects mainly via the activation of soluble guanylyl cyclase, but alternative signaling mechanisms, such as the activation of cyclooxygenase or the inhibition of cytochrome P450, have also been reported. In in vitro studies, the formation of CO within the hypothalamus has been associated with inhibition of the release of hormones such as corticotropin-releasing hormone, arginine vasopressin and oxytocin involved in hypothalamo-pituitary-adrenal axis activation and, conversely, with stimulation of luteinising hormone-releasing hormone release, thus suggesting that the gas may have a neuroendocrine role which may be to prevent over-exuberant activation of the hypothalamo-pituitary-adrenal axis and inhibition of reproductive processes within the hypothalamus during stress. At present, however, the possible pathophysiological relevance of the in vitro observations remains to be demonstrated.
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PMID:The role of carbon monoxide in the regulation of neuroendocrine function. 965 Aug 14

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

Cyclic guanosine monophosphate (cGMP), which is implicated in cardiac cell growth and function, is synthesized by cytoplasmic soluble guanylyl cyclase (GC) stimulated via nitric oxide (NO) and by particulate membrane-bound GC activated via natriuretic peptides. We investigated possible cGMP elevation in the left ventricle (LV) of rats developing physiologic LV hypertrophy during gestation. Furthermore, expression of estrogen receptors (ER) and oxytocin receptors (OTR) was evaluated because their activation stimulates NO and atrial natriuretic peptide (ANP) release from the heart. Compared with nonpregnant controls, Sprague-Dawley rats on day 7 of gestation had similar heart weights, but, on days 14 and 21, ventricular mass increased by 12% and 28% respectively (P< 0.05). LV cGMP concentration was elevated at day 14 of gestation (3.25 +/- 0.12 vs 4.65 +/- 0.17 pmol/g wet weight, P< 0.01) but decreased at day 21 (2.45 +/- 0.09 pmol/g, P< 0.05) to increase again on postpartum day 1 (6.01 +/- 0.15 pmol/g) and day 4 (9.21 +/- 1.79 pmol/g). Changes in endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), OTR and ERalpha, but not ERbeta, proteins paralleled the pregnancy-related cGMP changes in the LV. In contrast, ANP mRNA of the LV remained at control level throughout gestation but increased postpartum, whereas brain natriuretic peptide (BNP) expression declined at term and increased postpartum. The particulate GC natriuretic peptide receptors (GC-A and GC-B) transcripts were already lower at day 14 of gestation. Natriuretic peptide clearance receptor (NPR-C) transcript was not altered on days 7 and 14, but increased at term. We conclude that cGMP concentration in the rat LV is influenced by both NOS and natriuretic peptide systems and may be involved in the changes of LV contractility and hypertrophy that occur during rat gestation.
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PMID:Pregnancy alters nitric oxide synthase and natriuretic peptide systems in the rat left ventricle. 1564 97

Nitric oxide relaxes myometrium in a cGMP-independent manner. Although cGMP activates its cognate kinase, this is not required for the inhibitory effect of nitric oxide. Thus, nitric oxide-mediated cGMP elevation does not enjoy the same set of substrates as it does in other smooth muscles. To further understand the regulation of relaxation of uterine muscle by cGMP, we have studied the actions of peptide-mediated cGMP action in guinea pig myometrium. We used both functional and biochemical studies of the action of the particulate guanylyl cyclase activator uroguanylin and its receptor, particulate guanylyl cyclase type C, to address the relationship between cGMP elevation acting in the membrane signaling domain to that of the nonmembrane region of the cell. Uroguanylin relaxed oxytocin-induced contractions in a dose-dependent fashion only in pregnant myometrium. Both relaxation and cGMP accumulation after uroguanylin stimulation were blocked by the putative particulate guanylyl cyclase type C inhibitors 2-chloro-ATP and isatin (1H-indole-2,3-dione), but not by the soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-A]quinoxalin-1-one (ODQ). Uroguanylin stimulated cGMP accumulation only in the pregnant myometrium. Caveolin-1 expression increased in pregnancy toward term. In the caveolin-1-containing membrane domain, uroguanylin, but not the nitric-oxide donor, led to the elevation of cGMP that was insensitive to ODQ. Particulate guanylyl cyclase C was expressed and prouroguanylin was detected in pregnant myometrium. We conclude that a uroguanylin-particulate cyclase-cGMP relaxation pathway is present and cGMP is compartmented in myometrium. The agonist-mediated selectivity of relaxation to cGMP is of fundamental pharmacological interest in understanding signal transduction in smooth muscle.
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PMID:Agonist-specific compartmentation of cGMP action in myometrium. 2065 Oct 27

Bone marrow stem cells (BMSCs) express cardiac markers in vitro and in vivo upon induction. Cardiomyogenic differentiation of embryonic stem cells induced by oxytocin (OT) involves the nitric oxide (NO)-soluble guanylyl cyclase (sGC) pathway. Also, OT improved cardiomyogenic differentiation of porcine BMSCs (pBMSCs). Here, we document the role of NO pathway in OT-mediated cardiomyogenic differentiation of pBMSCs obtained from bone marrow aspirates of juvenile pigs. Cells were exposed (OT cells) or not (control cells) to OT, in presence or absence of a NO synthase inhibitor (L-NAME) and a sGC inhibitor (ODQ). Gene (RT-PCR) and protein expression (immunocytochemistry) of NOS was up-regulated after OT induction. Exposure of OT cells to L-NAME, ODQ, or both, leaded to a significant reduction in cardiac troponin I transcripts, and protein (Western Blot) expression. For the latter, ODQ looked more performing in inhibition than L-NAME. Expression of cardiac troponin T and myosin heavy chain (immunocytochemistry) was less abundant in OT cells exposed to inhibitors without apparent synergic effect between L-NAME and ODQ. In control cells, protein expression remained low. Moreover, OT-induced cell proliferation, and this effect was counteracted by NOS/sGC inhibitors. Inhibiting NO production and NO effector, sGC, affected the OT-mediated differentiation of pBMSCs, because abundance of cardiac proteins was reduced to levels similar to those observed in control cells. We propose that following treatment with OT, activation of NO pathway directs pBMSCs to a preferential cardiomyogenic phenotype and stimulates cell proliferation.
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PMID:Involvement of the nitric oxide-soluble guanylyl cyclase pathway in the oxytocin-mediated differentiation of porcine bone marrow stem cells into cardiomyocytes. 2093 29