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

The influence of propranolol, isoprenaline, papaverine and caffeine on basal tone and contractile responses to spasmogens (oxytocin, KCl) was investigated in the presence and the absence of external calcium in estrogen-treated rat uterus. Isoprenaline, papaverine and caffeine relaxed precontracted uterus and caffeine also decreased the basal tone of uterine muscle in calcium-containing or calcium-free solution. Propranolol had a dual activity in calcium-free medium: lower concentrations contracted the sustained contraction elicited by oxytocin, whereas the highest concentration partially relaxed it. In calcium-containing solution the highest dose of propranolol partially inhibited KCl-induced contractions.
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PMID:Different actions of some relaxant agents acting via the cAMP system in rat uterus. 762 19

The effects of okadaic acid (OA), a monocarboxylic acid produced by marine dinoflagellates belonging to the genera Dinophysis and Prorocentrum, and their interactions with theophylline and caffeine were studied on the rat-isolated uterus in a calcium-containing medium and a calcium-free medium in the presence of 10(-3) M EGTA. Okadaic acid (5 x 10(-6) to 5 x 10(-5) M) induced a concentration-dependent contraction of the rat-isolated uterus corresponding, with 5 x 10(-5) M, to 142.3 +/- 6.1% (n = 7) of the contraction induced by oxytocin 10(-6) M. The time to peak tension was inversely proportional to the maximum effect produced. The contraction was not sustained and was followed by a concentration-dependent decrease in tone. In a Ca(2+)-free medium containing 10(-3) M EGTA the contractile effects of OA were significantly inhibited or reduced. A 30 min pretreatment with theophylline (3 x 10(-3) M) or caffeine (2 x 10(-2) M) significantly reduced, in a Ca(2+)-containing medium, the maximum contractile effect of OA 10(-5) and/or 2 x 10(-5) M and shortened the relative time to peak tension. In a Ca(2+)-free medium containing 10(-3) M EGTA, only the second effect was observed. With a 1 min pretreatment and in a Ca(2+)-containing medium, theophylline 3 x 10(-3) M and caffeine 10(-2) M did not modify the maximum effect of OA 10(-5) M but shortened the time to peak tension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of calcium on the effects of okadaic acid and its interaction with caffeine and theophylline in rat myometrium. 782 49

Intracellular free Ca2+ concentration ([Ca2+]i) was monitored using the fluorescence from the dye Fura-2-AM in single myometrial cells from pregnant rats. Oxytocin and acetylcholine applied to the cell evoked an initial peak in [Ca2+]i followed by a smaller sustained rise which was rapidly terminated upon removal of acetylcholine or persisted after oxytocin removal. A Ca2+ channel blocker (oxodipine) and external Ca2+ removal decreased both the transient and sustained rises in [Ca2+]i suggesting that Ca2+ influx through L-type Ca2+ channels participated in the global Ca2+ response induced by oxytocin. However, the initial peak in [Ca2+]i produced by oxytocin was mainly due to Ca2+ store release: it was abolished by inclusion of heparin [which blocks inositol 1,4,5-trisphosphate (InsP3) receptors] in the pipette (whole-cell recording mode of patch-clamp) and external application of thapsigargin (which blocks sarcoplasmic reticulum Ca(2+)-ATPases). In contrast, the transient Ca2+ response induced by oxytocin was unaffected by ryanodine. Moreover, caffeine failed to induce a rise in [Ca2+]i but reduced the oxytocin-induced transient Ca2+ response. The later sustained rise in [Ca2+]i produced by oxytocin was due to the entry of Ca2+ into the cell as it was suppressed in external Ca(2+)-free solution. The Ca2+ entry pathway is permeable to Mn2+ ions, in contrast to that described in various vascular and visceral smooth muscle cells. Oxytocin-induced Ca2+ release is blocked by the oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT. The prolonged increase in [Ca2+]i after oxytocin removal is rapidly terminated by addition of the oxytocin antagonist suggesting that oxytocin dissociation from its receptor is very slow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin mobilizes calcium from a unique heparin-sensitive and thapsigargin-sensitive store in single myometrial cells from pregnant rats. 797 Nov 61

The properties of contractile elements and intracellular Ca2+ storage sites of pregnant human myometrium were studied by recording the mechanical responses in skinned (saponin-treated and membrane-permeable) fibres. Calmodulin increased the amplitude of contractions induced by Ca2+ and the Ca2+ sensitivity for contractile elements in small myometrium strips, but PGF2 alpha, PGE2, oxytocin, or cyclic AMP failed to produce similar effects. After accumulation of Ca2+ in intracellular Ca2+ storage sites, 10 mumol/l PGF2 alpha, 10 mumol/l PGE2, 30 mmol/l caffeine, and 20 mumol/l InsP3 (inositol-trisphosphate) produced contractions by releasing Ca2+ from storage sites. However, 20 nmol/l oxytocin had no effects under the same conditions. The InsP3 sensitive Ca2+ store was much larger than those of PGs or caffeine. These results suggest that pregnant human myometrium contracts with low Ca2+ by a calmodulin sensitive system. The data also indicate that direct application of PGF2 alpha, or PGE2 into the cells discharges Ca2+ from Ca2+ storage sites and that oxytocin extricates Ca2+ via a pathway involving InsP3 by activation of phosphoinositide turnover. We suggest that these agents induce added contractile responses due to a Ca2+ release mechanism from store sites in addition to the influx of Ca2+ from the extracellular space.
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PMID:Some mechanical properties of skinned fibres of pregnant human myometrium. 798 18

1. The intracellular Ca2+ concentration ([Ca2+]1) was monitored in single magnocellular neurones freshly isolated from rat supraoptic nucleus. Application of 100 nM vasopressin increased [Ca2+]1. Two types of [Ca2+]1 responses were observed: (i) a transient response, displayed by 86% of the vasopressin-sensitive neurones, and (ii) a sustained response displayed by 14% of the vasopressin-sensitive neurones. 2. Among responding neurones, 52% were vasopressin sensitive, 44% were oxytocin sensitive and 4% were sensitive to both peptides. 3. Responses to vasopressin were dose dependent, showed a progressive desensitization after successive applications, were specifically blocked by the V1a vasopressin receptor antagonist, SR 49059, and were unaffected by the oxytocin receptor antagonist, d(CH2)5OVT. 4. Vasopressin responses were completely suppressed by the removal of external Ca2+. 5. The intracellular Ca2+ mobilizers, caffeine and tBuBHQ, did not affect resting or vasopressin-induced [Ca2+]1 changes. Thapsigargin (200 nM) on its own evoked an increase in [Ca2+]1, and reduced the [Ca2+]1 increase evoked by vasopressin by 52%, suggesting that thapsigargin-sensitive Ca2+ stores are partially involved in the vasopressin response. 6. Immunocytochemical identification revealed that vasopressin-responding neurones synthesize vasopressin whereas oxytocin-responding neurones synthesize oxytocin. 7. In conclusion, vasopressin- (partially external Ca2+ dependent) and oxytocin (totally external Ca2+ independent)-induced [Ca2+]1 changes are mediated by specific receptors. In addition, vasopressin and oxytocin neurones are specifically autoregulated by their own peptides.
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PMID:Vasopressin-induced intracellular Ca2+ increase in isolated rat supraoptic cells. 868 70

The effect of the uterotonic pituitary hormone oxytocin on the regulation of intracellular calcium concentration ([Ca2+]i) was studied in single cells of a smooth muscle cell line derived from human non-pregnant myometrium. [Ca2+]i was measured with fluorescence microscopy, and by recording the activity of Ca(2+)-activated potassium currents (IK(Ca)) on the whole cell and single channel level. Oxytocin induced a rapid and transient increase in [Ca2+]i that was paralleled by a significant increase in IK(Ca) activity. After removal of extracellular Ca2+, repetitive stimulation with oxytocin did not alter the [Ca2+]i transients initially; however, their amplitude became progressively smaller and the response was eventually abolished completely, indicating that oxytocin increased [Ca2+]i by release of Ca2+ from intracellular stores. Nifedipine did not alter the oxytocin-induced [Ca2+]i-transients suggesting that oxytocin failed to activate Ca2+ entry through voltage-operated Ca2+ channels. Thapsigargin abolished the oxytocin-induced [Ca2+]i transient. Caffeine alone had no effect on [Ca2+]i, however it diminished the oxytocin-induced [Ca2+]i transients. Ryanodine did not affect the oxytocin response indicating that these cells lack release of Ca2+ from the ryanodine receptor release channel. These results demonstrate that oxytocin elicited [Ca2+]i transients predominantly through Ca2+ release from thapsigargin-sensitive stores, presumably by activating an inositol 1,4,5-trisphosphate dependent pathway.
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PMID:Characterization of an oxytocin-induced rise in [Ca2+]i in single human myometrium smooth muscle cells. 886 70

1. Oxytocin is known to act on autoreceptors of oxytocin neurones in the supraoptic nucleus (SON). We investigated whether oxytocin modulates putative oxytocin neurones by suppressing the GABAA receptor-mediated synaptic inputs on these cells. 2. GABAergic inhibitory postsynaptic currents (IPSCs) were recorded from SON neurones in hypothalamic slices from young rats. Oxytocin specifically reduced the amplitude of both spontaneous and evoked IPSCs, without altering their current kinetics. 3. The effect of oxytocin was observed in 70% of the magnocellular neurones recorded from the dorsomedial part of the SON. d(CH2)5OVT, a specific antagonist of oxytocin receptors, blocked the effect of oxytocin on the IPSCs. Vasopressin had no effect on oxytocin-sensitive SON neurones. 4. The intervals between spontaneous IPSCs were not affected by oxytocin. This suggested that oxytocin had a postsynaptic effect on SON neurones. 5. This postsynaptic origin was further substantiated by application of TTX, which blocked all evoked release but did not prevent the suppressive effect of oxytocin on the amplitude of the spontaneous IPSCs still present in the recording. The selective effect of oxytocin on IPSC amplitude was also maintained in nominally zero extracellular calcium. 6. Intracellular perfusion of SON neurones with GTP gamma S mimicked the effect of oxytocin on IPSCs, while GDP beta S, similarly applied, abolished the effect of oxytocin. 7. Application of calcium mobilizers such as thapsigargin and caffeine also reduced the amplitude of spontaneous IPSCs without significantly altering the frequency at which IPSCs occurred. 8. Thus, oxytocin depresses GABAergic synapses in the SON via modulation of the postsynaptic GABAA receptors. This would lead to disinhibition of SON neurones sensitive to oxytocin and could, therefore, be a powerful means of controlling the firing of oxytocin neurones.
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PMID:Postsynaptic mechanism of depression of GABAergic synapses by oxytocin in the supraoptic nucleus of immature rat. 896 Nov 90

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

Subtype 3 of the ryanodine receptor (RYR3) is a ubiquitous Ca2+ release channel which is predominantly expressed in smooth muscle tissues and certain regions of the brain. We show by reverse transcription-polymerase chain reaction (RT-PCR) that non-pregnant mouse myometrial cells expressed only RYR3 and therefore could be a good model for studying the role of endogenous RYR3. Expression of RYR3 was confirmed by Western blotting and immunostaining. Confocal Ca2+ measurements revealed that in 1.7 mM extracellular Ca2+, neither caffeine nor photolysis of caged Ca2+ were able to trigger any Ca2+ responses, whereas in the same cells oxytocin activated propagated Ca2+ waves. However, under conditions of increased sarcoplasmic reticulum (SR) Ca2+ loading, brought about by superfusing myometrial cells in 10 mM extracellular Ca2+, all the myometrial cells responded to caffeine and photolysis of caged Ca2+, indicating that it was possible to activate RYR3. The caffeine-induced Ca2+ responses were inhibited by intracellular application of an anti-RYR3-specific antibody. Immunodetection of RYR3 with the same antibody revealed a rather homogeneous distribution of fluorescence in confocal cell sections. In agreement with these observations, spontaneous or triggered Ca2+ sparks were not detected. In conclusion, our results suggest that under conditions of increased SR Ca2+ loading, endogenous RYR3 may contribute to the Ca2+ responses of myometrial cells.
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PMID:Identification and function of ryanodine receptor subtype 3 in non-pregnant mouse myometrial cells. 1182 55

The importance of intracellular calcium ([Ca2+]i) in the release of vasopressin (AVP) and oxytocin from the central nervous system neurohypopyhysial nerve terminals has been well-documented. To date, there is no clear understanding of Ca2+ clearance mechanisms and their interplay with transmembrane Ca2+ entry, intracellular [Ca2+]i transients, cytoplasmic Ca2+ stores and hence the release of AVP at the level of a single nerve terminal. Here, we studied the mechanism of Ca2+ clearance in freshly isolated nerve terminals of the rat neurohypophysis using Fura-2 Ca2+ imaging and measured the release of AVP by radioimmuno assay. An increase in the K+ concentration in the perfusion solution from 5 to 50 mM caused a rapid increase in [Ca2+]i and AVP release. Returning K+ concentration to 5 mM led to rapid restoration of both responses to basal level. The K+-evoked [Ca2+]i and AVP increase was concentration-dependent, reliable, and remained of constant amplitude and time course upon successive applications. Extracellular Ca2+ removal completely abolished the K+-evoked responses. The recovery phase was not affected upon replacement of NaCl with sucrose or drugs known to act on intracellular Ca2+ stores such as thapsigargin, cyclopiazonic acid, caffeine or a combination of caffeine and ryanodine did not affect either resting or K+-evoked [Ca2+]i or AVP release. By contrast, the plasma membrane Ca2+ pump inhibitor, La3+, markedly slowed down the recovery phase. The mitochondrial respiration uncoupler, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), slightly but significantly increased the basal [Ca2+]i, and also slowed down the recovery phase of both [Ca2+]i and release responses. In conclusion, we show in nerve terminals that (i) Ca2+ extrusion through the Ca2+ pump in the plasma membrane plays a major role in the Ca2+ clearance mechanisms of (ii) Ca2+ uptake by mitochondria also contributes to the Ca2+ clearance and (iii) neither Na+/Ca2+ exchangers nor Ca2+ stores are involved in the Ca2+ clearance or in the maintenance of basal [Ca2+]i or release of AVP.
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PMID:Ca2+ clearance mechanisms in neurohypophysial terminals of the rat. 1554 63


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