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

In adipocytes that have been deprived of growth hormone (GH) for at least 3 hr, GH elicits a transient insulin-like response that is followed by a period of refractoriness to further insulin-like stimulation. Exposure of adipocytes to GH in the first hour of a 3-hr incubation prevents the appearance of insulin-like sensitivity. Intracellular Ca2+ concentration [( Ca2+]i) was measured in individual adipocytes that were loaded with fura-2 hexakis(acetoxymethyl) ester after preincubation in the presence (refractory) or absence (sensitive) of recombinant human GH at 100 ng/ml. Using a dual nitrogen laser imaging microscope with computer-assisted image processing to measure fluorescence changes, we observed that resting [Ca2+]i was 220 +/- 10 nM in refractory adipocytes and 110 +/- 6 nM in sensitive adipocytes (P less than 0.001). GH had no acute effect on [Ca2+]i in sensitive adipocytes but caused a sustained 3-fold increase in [Ca2+]i in refractory cells within 3 min (P less than 0.001). Insulin did not change [Ca2+]i in either sensitive or refractory adipocytes. In refractory cells treated with insulin and GH simultaneously, insulin completely blocked the rise in [Ca2+]i due to GH. Oxytocin elicited a prompt increase in [Ca2+]i followed by a quick return to resting levels in both sensitive and refractory cells. These findings indicate that basal [Ca2+]i is increased in refractory cells and that GH produces a sustained rise in [Ca2+]i only in refractory adipocytes. We suggest that the sustained increase in [Ca2+]i produced by GH in refractory cells prevents the expression of the insulin-like response.
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PMID:Refractoriness to growth hormone is associated with increased intracellular calcium in rat adipocytes. 186 2

1. We studied the effects of extracellular sodium on the secretion of vasopressin (VP) and oxytocin (OT) and the efflux of 45Ca from isolated, perfused nerve endings of the rat neurohypophysis (neurosecretosomes). 2. Upon removal of sodium from the perfusing medium, basal release of VP and OT increased by 3.95 +/- 0.23- and 3.71 +/- 0.22-fold, respectively, followed by a decline to about double the levels in normal (150 mM) sodium (P less than or equal to 0.1). 3. Compared to neurosecretosomes perfused in normal (150 mM) sodium, omission of sodium from the medium augmented ionomycin-induced VP and OT secretion by 66 +/- 5- and 20 +/- 3-fold, respectively, and A23187-induced secretion was increased 1.3 +/- 0.4- and 1.3 +/- 0.1-fold (P less than or equal to 0.01 for both ionophores). 4. The inhibition of ionomycin-induced secretion by sodium was concentration dependent (P less than or equal to 0.01 for sodium greater than or equal to 5 mM); the IC50 was about 10 mM sodium for both hormones, and the Hill slope was close to -1. 5. The rate of 45Ca efflux from neurosecretosomes showed 2.7 +/- 0.1-fold stimulation upon increasing sodium from 4.5 to 150 mM (P less than or equal to 0.01). 6. Our results suggest that sodium inhibits basal and stimulated secretion at the nerve terminal, possibly by reducing intraterminal calcium through sodium/calcium exchange.
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PMID:Sodium inhibits hormone release and stimulates calcium efflux from isolated nerve endings of the rat neurohypophysis. 186 7

The synthesis and release of PRL are regulated by a variety of factors that originate in the hypothalamus, peripheral tissues, or posterior pituitary (PP). We recently reported that coculture of anterior pituitary (AP) and PP cells induced an increase in both PRL cell content and the responsiveness of lactotrophs to TRH. The aim of the present study was to determine whether the augmented response to TRH is due to increased lactotroph sensitivity to this particular secretagogue or to enhancement of the releasable pool of PRL. Cells obtained from anterior pituitaries of adult male rats were plated either alone or together with PP cells at the same total density. Cells cultures were maintained in serum-free medium for 4 days and then incubated for 20 min with the designated substances. Angiotensin-II and TRH evoked a significantly larger release of PRL in AP + PP cocultures than in AP cells cultured alone; the greatest difference between the culture types was observed at the highest concentrations of both secretagogues. The stimulation of PRL release by KCl, the calcium ionophore A23187, and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate was higher in the presence of PP cells than in cultures of AP cells alone, although the magnitude of this effect was lower than that seen with PRL secretagogues. The concomitant application of A23187 and 12-O-tetradecanoylphorbol-13-acetate resulted in an increased response in both types of culture and a greater relative effect of PP cells on the evoked PRL release. In contrast to other secretagogues, oxytocin (OT) elicited a smaller response in AP + PP cocultures than in AP cultures. OT was present in significant amounts in medium from cocultures, apparently after being released from the severed neuronal terminals. When AP cultures were pretreated for 4 days with comparable concentrations of OT, the acute OT-evoked PRL release was greatly diminished. These findings suggest that coculture with PP cells increases the releasable pool of PRL in lactotrophs. The stored PRL is accessible for release by secretagogues known to act via the Ca2+ second messenger system, involving both Ca2+/calmodulin and protein kinase-C pathways. The diminished response of cocultures to OT is probably due to desensitization of lactotrophs by the residual amounts of this peptide present in the disrupted nerve endings.
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PMID:Effects of coculture of anterior and posterior pituitary cells on the responsiveness of lactotrophs to different secretagogues. 193 84

1. The effect of tetrodotoxin (5 microM), monensin (10 microM) and the replacement of Na+ by choline (choline medium) on the contractions of the rat testicular capsule induced by oxytocin (50 and 200 nM) have been studied. 2. The sodium channel blocker tetrodotoxin did not modify the oxytocin contraction. 3. The sodium ionophore monensin produces contraction of rat testicular capsule and reduces the oxytocin-induced contraction. The monensin contraction is inhibited by amiloride (0.1 mM). 4. Replacement of Na+ by choline increases the contraction induced by oxytocin and KCl (60 mM) but inhibits that induced by noradrenaline (3 microM). 5. The increase of contraction due to oxytocin in choline medium is inhibited by amiloride (50 microM and 1 mM) and when calcium is suppressed of the incubation medium.
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PMID:Influences of sodium on the contraction induced by oxytocin in rat testicular capsule. 193 6

We previously reported that prolactin (PRL) could increase the activity of ornithine decarboxylase (ODC) in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). This action of the hormone was inhibited by oxytocin (OT), the calcium ionophore A23187, and diacyglycerol (DG) and was duplicated by 10 microM verapamil (VML), a calcium channel blocker. Here, we expand these results to show that 1) a higher dose of VML (50 microM) produces an additive effect with PRL; 2) addition of small amounts of calcium (0.1 mM) to the liver culture medium blocks PRL action; 3) neither nifedipine (NIF), a different type of calcium channel blocker, nor EDTA alter PRL action; and 4) gossypol, a reported inhibitor of protein kinase C, mimics PRL action. Additionally, we show that PRL increases ODC activity in tiger salamander tail skin in vitro, a tissue previously demonstrated to be a PRL target tissue in this species. The same set of treatments which we have shown to modify PRL effects on ODC in liver slices affects PRL action in the tail skin in a parallel manner. Thus, the mechanism whereby PRL enhances ODC activity appears to be the same in both these tissues. These results are discussed in conjunction with the findings from similar studies using mammalian tissues in an attempt to assess the current picture of the mechanism of PRL action and the possible role of inositol phospholipid turnover, calcium, and protein kinase C in the action of this hormone.
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PMID:Reduced calcium and inhibition of protein kinase C mimic the enhancement of ornithine decarboxylase activity of prolactin in Ambystoma tigrinum tissues. 194 Aug 22

The effects of EtOH on peptide release and on high-threshold, voltage-activated calcium (Ca++) channels were examined in acutely dissociated rat neurohypophysial terminals. These terminals release the peptide hormones, arginine vasopressin (AVP) and oxytocin. Release of AVP from isolated intact neurohypophyses, induced by either electrical stimulation or elevated potassium, was inhibited by clinically relevant concentrations of EtOH. "Whole-cell" patch-clamp recording methods were used to study the effects of EtOH on voltage-activated Ca++ currents (ICa) in the peptidergic nerve terminals. Amplitudes of both fast-inactivating ICa and long-lasting ICa were reduced in EtOH, and the reduction in ICa did not result from a shift in its current-voltage or steady-state inactivation relationships. Only the fast-inactivating component recovered after removal of EtOH. The effects of EtOH on ICa could not be attributed to changes in osmolarity. In contrast to ICa, the fast, transient K+ current was insensitive to EtOH. These results suggest that EtOH-induced reduction of ICa in the peptidergic nerve terminals produces a decrease in AVP release, resulting in lowered plasma AVP levels.
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PMID:Calcium currents and peptide release from neurohypophysial terminals are inhibited by ethanol. 194 19

Preincubation of Fura 2-loaded rat myometrial cells with H-8, an inhibitor of protein kinase A, for 1 h reversed the inhibitory effects of 8-(4-chlorophenylthio)-cAMP (CPTcAMP) on the oxytocin-stimulated increase in (Ca2+)i (intracellular free calcium), with an EC50 of 47 microM. H-8 also prevented the inhibition by relaxin and isoproterenol of the oxytocin-induced increase in (Ca2+)i. The EC50 of H-8 in reversing the relaxin effect was 42 microM. H-8 reversal of the effect of relaxin on (Ca2+)i was evident both in the absence of extracellular calcium and in cells pretreated with pertussis toxin. H-8 also reversed the inhibitory effects of relaxin and CPTcAMP on the oxytocin-induced increase in [3H]inositol phosphate formation and [3H]phosphoinositide hydrolysis. Preincubation of myometrial cells for 1 h with H-7, another protein kinase inhibitor, only partially attenuated the inhibition by relaxin and CPTcAMP of the oxytocin-induced increase in (Ca2+)i and [3H]inositol phosphate formation at concentrations 4-5 times greater than those of H-8. Acute (15-min) exposure to phorbol myristate acetate (1.0 microM) did not affect basal (Ca2+)i or the oxytocin-stimulated increases in (Ca2+)i or inositol phosphate formation. These results imply a regulatory role for protein kinase A in the inhibition of the oxytocin-induced increase in (Ca2+)i and inositol phosphate formation by relaxants.
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PMID:Involvement of protein kinase A in the regulation of intracellular free calcium and phosphoinositide turnover in rat myometrium. 196 19

The changes in intracellular free calcium concentration ([Ca2+]i) induced by oxytocin in single cells of cultured human puerperal myometrium were measured with the calcium-sensitive fluorescent dye fura 2 in a digital imaging fluorescence microscopic system. Oxytocin at concentrations of 30-300 nmol/L induced a dose-dependent increase in [Ca2+]i with a peak at 20 seconds. This increase depended mainly on extracellular calcium ([Ca2+]ex) at concentrations of 0.6-4.8 mmol/L. In the absence of [Ca2+]ex, the increase was only 16% of that in its presence. The voltage-sensitive calcium channel blockers nicardipine, nifedipine, and nitrendipine had similar effects, causing significant suppression of the increase in [Ca2+]i induced by oxytocin. Diltiazem also suppressed the increase in [Ca2+]i, though less than the other calcium channel blockers. These data indicate that the increase in [Ca2+]i induced by oxytocin is predominantly dependent upon [Ca2+]ex. Furthermore, the data explain why calcium channel blockers are effective for weakening uterine muscle contractions and indicate which type of blocker is most effective.
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PMID:Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: effects of extracellular calcium and calcium channel blockers. 198 7

In previous work we reported that oxytocin activates phospholipase-C (PLC) and increases prostaglandin E2 (PGE2) release in amnion. Whether either of the consequences of activation of PLC by oxytocin, activation of protein kinase-C (PKC) or increases in intracellular calcium, directly results in the production of PGE2 is unknown. Phorbol esters (PMA) and epidermal growth factor (EGF) are also known to increase PGE2 release from amnion. In some tissues these agents are capable of activating the PLC postreceptor cascade system. This study was undertaken primarily to explore the mechanism of oxytocin-induced PGE2 production in amnion and secondarily to determine whether common aspects of PGE2 production by oxytocin, PMA, and EGF include activation of PLC or subsequent steps in this cascade followed by new mRNA/protein production. Involvement of PLC was assessed by inositol phosphate (IP1) turnover. IP1 turnover was increased by oxytocin (2.99 +/- 0.31-fold; P less than 0.01), but not by EGF or PMA. PMA inhibited oxytocin-provoked IP1 turnover (P less than 0.05). PKC involvement was initially evaluated with two PKC inhibitors, H7 and staurosporine. Each inhibited PGE2 production by oxytocin as well as that by PMA and EGF in a dose-dependent fashion. With H7, the IC50 for all agents was 5 microM; the IC50 for staurosporine was 2 nM for PMA and oxytocin and 5 nM for EGF. Agonist-induced PGE2 production was also assessed in cells in which PKC activity had been tachyphylaxed with a high concentration of PMA (400 ng/mL for 48 h). In such cells oxytocin and PMA no longer stimulated (P less than 0.001) PGE2 production, but EGF-stimulated PGE2 production was only slightly reduced. PKC involvement is, thus, implicated for oxytocin and PMA. Other enzymes that are inhibited by H7 and staurosporine are implicated in the production of PGE2 caused by EGF. Although tachyphylaxed cells produced no PGE2 with oxytocin, oxytocin increased intracellular calcium to levels higher than those seen in control cells (435 +/- 102 vs. 286 +/- 1.2) Actinomycin-D (P less than 0.001) and cycloheximide (P less than 0.05) inhibited PGE2 production caused by oxytocin, PMA, and EGF. PGE2 production by oxytocin in human amnion cells proceeds by activation of PKC, followed by new protein and mRNA production. Further, in cells without PKC, oxytocin-induced calcium transients do not increase PGE2. The ability of EGF to stimulate PGE2 in cells with no PKC activity also establishes that PKC activation is not a common intracellular step in the induction of PGE2 production by all agents.
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PMID:Protein kinase-C activation is required for oxytocin-induced prostaglandin production in human amnion cells. 202 8

1. Magnocellular neuroendocrine cells (MNCs) in the supraoptic nucleus (SON) of mammals synthesize vasopressin or oxytocin and release these hormones systemically from their neurohypophysial axon terminals. In the rat, release is facilitated by bursts of action potentials generated by the MNC. However MNC units in the intact cat discharge more slowly and do not display the repetitive bursts (phasic firing) that promote vasopressin secretion. The reasons why these cat endocrine neurones differ so dramatically in their firing behaviour from the rat model were examined using intracellular recording. 2. Cat and rat MNCs displayed similar mean resting potentials approximating -60 mV, and were usually linear in their voltage-current relationship in the hyperpolarizing direction. However cat MNCs displayed a higher mean cell input resistance (301 M omega; n = 56) than those of rat (150 M omega; n = 105). 3. Calcium influx to cat MNCs during firing appeared comparable to rat based on (a) the similar range of action potential broadening observed during a spike train, (b) the shoulder on the action potential's falling phase which was blocked in low-Ca2+ saline, and (c) the ability to evoke tetrodotoxin (TTX)-insensitive spiking and non-synaptic depolarizing potentials, both calcium-mediated events observed in the rat. 4. In cat MNCs, a depolarizing current pulse (100-500 ms; 0.1-0.3 nA) elicited a train of action potentials followed by a prominent after-hyperpolarization (AHP) several times the duration of its counterpart in the rat. The AHP reversed near the equilibrium potential for K+, was not voltage dependent and represented an increased membrane conductance. It was suppressed in low-Ca2+ saline and completely eliminated by the calcium-activated potassium current (IK(Ca)) blockers apamin (100 nM) or d-tubocurarine (50-200 microM). Both blockers decreased spike frequency adaptation but did not induce bursting. Therefore the cat AHP probably represents a Ca(2+)-activated K+ conductance with a similar blocker sensitivity to its briefer counterpart in the rat MNC. 5. The spike hyperpolarizing after-potentials (HAPs) in cat were more than twice the mean amplitude and several times the duration of HAPs in rat. Cat HAPs were qualitatively similar to their rat counterparts, remaining unaffected by apamin or tubocurarine. The intrinsic currents responsible for the AHP and HAP appear to generate the stronger activity-dependent inhibition displayed by cat MNCs. 6. Twenty-one of fifty-two cat MNCs displayed an inward rectification at membrane potentials more negative than -70 mV ([K+]o = 6.24 mM), causing a depolarizing 'sag' in the voltage trajectory lasting 100-200 ms which was TTX resistant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intracellular study of calcium-related events in cat magnocellular neuroendocrine cells. 202 22


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