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)

Plasma natriuretic activity was evoked in cows and dogs by infusion of saline with or without dextran. Deproteinized samples were fractionated on both Sephadex and Bio-Gel columns; the activity was separated, the approximate molecular weight being in the region of 1000. Incubation with chymotrypsin destroyed the activity, suggesting that it might be a polypeptide. A similar activity in blood resulted from intracarotid injection of either oxytocin or either of two synthetic analogs. Possibly the latter are saluretic by virtue of a releasing action on some intracranial structure for another natriuretic peptide.
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PMID:Plasma saluretic activity: its nature and relation to oxytocin analogs. 577 12

We investigated the ultracytochemical localization of particulate guanylate cyclase (GC) in the rat neurohypophysis after activation with rat atrial natriuretic factor (rANF) or porcine brain natriuretic peptide (pBNP). Under our experimental conditions, the presence of GC reaction product indicated that rANF and pBNP were strong activators of particulate GC since samples incubated in basal conditions without rANF or pBNP did not reveal any GC reaction product. The rANF-stimulated GC was localized both to pituicytes and to nerve fibers and endings whereas the pBNP-stimulated GC was present exclusively in nerve fibers and endings. Recently, two subtypes of receptors for natriuretic peptides have been identified as two isoforms of particulate GC [24,50]. Our data indicate that the receptors of the two hormones have a partially distinct distribution in the rat neurohypophysis. In pituicytes, GC reaction product was found on plasma membrane of finger-like processes and on the membranes surrounding the lipid droplets. In nerve fibers and endings, GC reaction product was associated with intracellular membranes. This finding suggests that the enzyme could mediate an internal inhibitory action of these hormones on the release of vasopressin and oxytocin.
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PMID:Detection of particulate guanylate cyclase in rat neurohypophysis after stimulation with ANF and BNP: an ultracytochemical study. 791 1

The cardiovascular-related peptides, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and endothelin (ET) were originally isolated from the atrium, brain and endothelial cells, respectively. ANP and BNP have hypotensive, natriuretic, diuretic and vasodilator effects. ET has strong vasoconstrictor effects. Centrally applied ANP and BNP attenuate pressure and drinking responses and vasopressin secretion induced by angiotensin II. Similar application of ET increases blood pressure in vivo and vasopressin secretion in vitro. To clarify direct effects of these peptides on neurons in the regions involved in body water homeostasis, extracellular recordings were made from neurons in the supraoptic nucleus (SON) and regions of anteroventral third ventricle (AV3V) of rat hypothalamic slice preparations. ANP and BNP inhibited AV3V neurons, suggesting direct actions of the peptides on drinking. In the SON, these peptides inhibited selectively putative vasopressin neurons but not putative oxytocin neurons, suggesting direct actions of the peptides on vasopressin secretion. We demonstrated that the inhibitory response by ANP and BNP is mediated through a second messenger cGMP system but not cAMP. Contrary to natriuretic peptides, ET excited AV3V neurons but inhibited SON neurons. Roles of ANP, BNP and ET on the central regulatory systems of body water homeostasis, acting as neurotransmitters or neuromodulators, will be discussed.
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PMID:Cardiovascular-related peptides influence hypothalamic neurons involved in control of body water homeostasis. 865 64

The effects of natriuretic peptides on electrical activity and cellular cGMP levels were studied in neurons of the supraoptic nucleus (SON) of rat hypothalamic slice preparations. Intracellular and extracellular recordings showed that bath application of A type natriuretic peptide (ANP) at 100 nM or B type natriuretic peptide (BNP) at 100 to 300 nM decreased the firing rate and hyperpolarized the membrane potential in phasically firing (putative vasopressin) neurons. Non-phasically firing (putative oxytocin) neurons did not respond to these natriuretic peptides in firing rate or membrane potential. The membrane-permeable cGMP analogue 8-bromo cGMP at 0.5 mM and the phosphodiesterase inhibitor 3/isobutyl-1-methylxanthine (IBMX) at 50 microM mimicked the inhibitory effects of ANP and BNP. The specific inhibitor of cGMP phosphodiesterase 1-(3-chloroanilino)-4-phenylphthalazine+ ++ (MY5445) at 30 microM also decreased the firing rate of SON neurons. The cGMP-dependent protein kinase inhibitor N-(2-(methylamino)ethyl)-5-isoquinoline-sulfonamide dihydrochloride (H8) at 1 microM abolished the inhibition by natriuretic peptides. We measured cGMP and cAMP contents in discrete SON regions and compared the change of contents before and after application of ANP and BNP. The increases in cellular cGMP accumulation were 430% for ANP and 120% for BNP, although they did not cause significant change of cAMP accumulation. The results suggest that the inhibitory effects of natriuretic peptides on putative vasopressin neurons are mediated through cGMP and cGMP-dependent protein kinase.
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PMID:Inhibitory effects of natriuretic peptides on vasopressin neurons mediated through cGMP and cGMP-dependent protein kinase in vitro. 868 Apr 19

Atrial natriuretic peptide (ANP) and its receptors are present in hypothalamic nuclei containing the magnocellular neurosecretory cells (MNCs), which release vasopressin and oxytocin. In the rat, intracerebroventricular injections of ANP inhibit the release of both hormones in response to hypertonicity. Although these findings suggest a role for endogenous ANP in the central control of fluid balance, cellular mechanisms underlying the modulatory actions of ANP are unknown. We therefore examined the effects of ANP on the osmoresponsiveness of MNCs impaled in rat hypothalamic explants. Applications of ANP (75-150 nM) over the supraoptic nucleus did not affect depolarizing responses to local hypertonicity, but they reversibly abolished the synaptic excitation of MNCs after hypertonic stimulation of the organum vasculosum laminae terminalis (OVLT). These effects were associated with decreased spontaneous EPSP (sEPSP) amplitude rather than with changes in sEPSP frequency. Accordingly, application of ANP reduced the amplitude of glutamatergic EPSPs evoked by electrical stimulation of the OVLT (IC50 approximately 3 nM). The inhibitory effects of ANP on EPSP amplitude were mimicked by application of 3'-5'-dibutyryl cGMP, consistent with the guanylate cyclase activity of natriuretic peptide receptors. Although depolarizing responses of MNCs to ionotropic glutamate receptor agonists were unaffected by ANP, the peptide reversibly enhanced paired-pulse facilitation of electrically evoked EPSPs. These results indicate that centrally released ANP may inhibit osmotically evoked neurohypophysial hormone release through presynaptic inhibition of glutamate release from osmoreceptor afferents derived from the OVLT.
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PMID:Atrial natriuretic peptide modulates synaptic transmission from osmoreceptor afferents to the supraoptic nucleus. 892 8

Previous studies indicated that the central nervous system induces release of the cardiac hormone atrial natriuretic peptide (ANP) by release of oxytocin from the neurohypophysis. The presence of specific transcripts for the oxytocin receptor was demonstrated in all chambers of the heart by amplification of cDNA by the PCR using specific oligonucleotide primers. Oxytocin receptor mRNA content in the heart is 10 times lower than in the uterus of female rats. Oxytocin receptor transcripts were demonstrated by in situ hybridization in atrial and ventricular sections and confirmed by competitive binding assay using frozen heart sections. Perfusion of female rat hearts for 25 min with Krebs-Henseleit buffer resulted in nearly constant release of ANP. Addition of oxytocin (10(-6) M) significantly stimulated ANP release, and an oxytocin receptor antagonist (10(-7) and 10(-6) M) caused dose-related inhibition of oxytocin-induced ANP release and in the last few minutes of perfusion decreased ANP release below that in control hearts, suggesting that intracardiac oxytocin stimulates ANP release. In contrast, brain natriuretic peptide release was unaltered by oxytocin. During perfusion, heart rate decreased gradually and it was further decreased significantly by oxytocin (10(-6) M). This decrease was totally reversed by the oxytocin antagonist (10(-6) M) indicating that oxytocin released ANP that directly slowed the heart, probably by release of cyclic GMP. The results indicate that oxytocin receptors mediate the action of oxytocin to release ANP, which slows the heart and reduces its force of contraction to produce a rapid reduction in circulating blood volume.
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PMID:Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart. 932 74

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

We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in mid-gestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1.5- to 2-fold postpartum (P<0.01). At term, ANP content in right (8.7+/-1.2 vs 12.7+/-1.1 micro g/mg protein, P<0.04) and left (3.5+/-0.6 vs 8.5+/-2.0 micro g/mg protein, P<0.01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2- and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.
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PMID:Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum. 1237 5

Previous work on the whole neurohypophysis has shown that hypotonic conditions increase release of taurine from neurohypophysial astrocytes (pituicytes). The present work confirms that taurine is present in cultured pituicytes, and that its specific release increases in response to a hypotonic shock. We next show that vasopressin (VP) and oxytocin (OT) also specifically release taurine from pituicytes. With an EC(50) of approximately 2 nm, VP is much more potent than OT, and the effects of both hormones are blocked by SR 49059, a V(1a) receptor antagonist. This pharmacological profile matches the one for VP- and OT-evoked calcium signals in pituicytes, consistent with the fact that VP-induced taurine efflux is blocked by BAPTA-AM. However, BAPTA-AM also blocks the taurine efflux induced by a 270 mosmol l(-1) challenge, which per se does not evoke any calcium signal, suggesting a permissive role for calcium in this case. Nevertheless, the fact that structurally unrelated calcium-mobilizing agents and ionomycin are able to induce taurine efflux suggests that calcium may also play a signalling role in this event. It is widely accepted that in hypotonic conditions taurine exits cells through anionic channels. Antagonism by the chloride channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) suggests the same pathway for VP-induced taurine efflux, which is also blocked in hypertonic conditions (330 mosmol l(-1)). Moreover, it is likely that the osmosensitivity of the taurine channel is up-regulated by calcium. These results, together with our in situ experiments showing stimulation of taurine release by endogenous VP, strengthen the concept of a glial control of neurohormone output.
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PMID:Vasopressin-induced taurine efflux from rat pituicytes: a potential negative feedback for hormone secretion. 1461 76

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


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