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

1. The characteristics of vasopressin-stimulated phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) and phosphatidylcholine (PtdCh) hydrolysis were examined in A10 vascular smooth muscle cells (VSMC), by assessing the formation of [3H]-inositol phosphates ([3H]-IP) and the accumulation of the phospholipase D (PLD) specific product, [3H]-phosphatidylbutanol ([3H]-PtdBuOH). 2. Vasopressin ([Arg8]-VP) and a number of related analogues stimulated the accumulation of [3H]-IP and [3H]-PtdBuOH with similar EC50 values, generating the same rank order of potency for each response (Arg8-VP = vasotocin = Lys8-VP much greater than oxytocin). 3. Inhibition of vasopressin-stimulated [3H]-IP and [3H]-PtdBuOH accumulation by the V1a receptor antagonists, Des-Gly9[beta-mercapto-beta,beta,-cyclopentamethylene propionyl, O-Et-Tyr2,Val4,Arg8]-vasopressin generated similar IC50 values suggesting that both these responses are mediated through the activation of a single V1a receptor subtype. 4. The onset of vasopressin-stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) mass formation preceded [3H]-PtdBuOH accumulation indicating that PtdCh hydrolysis was activated subsequent to PtdIns(4,5)P2 breakdown. 5. The protein kinase C (PKC) activator, tetradecanoylphorbol acetate (TPA) also stimulated [3H]-PtdBuOH accumulation. Preincubation with the PKC inhibitor Ro-31-8220 abolished both TPA- and vasopressin-stimulated [3H]-PtdBuOH, suggesting that the intermediate activation of protein kinase C is involved in the regulation of PLD by vasopressin. 6. Pretreatment of the A10 VSMC with Ro-31-8220 (100 microM) also potentiated vasopressin-stimulated Ins(1,4,5)P3 mass formation.Therefore stimulation of PKC may have opposing roles in the regulation of agonist activation of PLC and PLD.7. Preincubation of the cells with EGTA, verapamil, or the receptor-operated calcium channel antagonist, SK&F 96365, reduced vasopressin-stimulated [3H]-PtdBuOH accumulation by approximately 30%, suggesting that influx of calcium has a significant role to play in the regulation of vasopressinstimulated PLD activity.
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PMID:Vasopressin-stimulated [3H]-inositol phosphate and [3H]-phosphatidylbutanol accumulation in A10 vascular smooth muscle cells. 133 Jan 54

The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S,1'S tetrandrine and its isomer 1R,1'S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca(2+)-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversible manner whilst only isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant activity as a calcium entry blocker.
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PMID:Tetrandrine and isotetrandrine, two bisbenzyltetrahydroisoquinoline alkaloids from Menispermaceae, with rat uterine smooth muscle relaxant activity. 135 38

The central nervous system modulates cardiovascular function and fluid and electrolyte balance in part through the actions of vasoactive peptides/neurotransmitters. The presence of several vasoactive peptides and their receptors in the hypothalamus suggests a possible interaction at this site. One level at which vasoactive peptides such as arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) might interact is through the mutual regulation of production and secretion in the hypothalamus. To determine whether AVP modulates ANP gene expression and secretion, we cultured fetal rat diencephalic neurons in the presence of AVP. AVP induced a significant increase in ANP secretion in dose-related fashion (mean +/- SEM basal ANP, 87 +/- 4 pg/ml; maximal mean AVP-stimulated ANP, 146 +/- 6 pg/ml; P less than 0.05, by analysis of variance). Neither oxytocin nor the vasoactive neuropeptide angiotensin-II had any effect on ANP secretion. The stimulatory effect of AVP was significantly blocked by coincubation with a V1 receptor antagonist, but was unaffected by a V2 receptor antagonist. The immunoreactive ANP secreted in response to AVP was the major brain isoform, ANP-(103-126). Coincubation with a calcium channel antagonist, nifedipine, had no effect on AVP-induced ANP secretion, while ryanodine, an inhibitor of intracellular calcium mobilization, significantly reduced the stimulatory effect of AVP. AVP induced a dose-related, nearly 3-fold maximal increase in ANP mRNA expression at 4 h. Coincubation of the neurons with a V1 receptor antagonist also significantly attenuated the increased ANP gene expression induced by AVP. These results indicate that AVP acts directly through V1 receptors on cultured fetal rat diencephalic neurons to augment ANP gene expression and secretion of the peptide. The effects are probably related to AVP-stimulated mobilization of intracellular calcium and not the result of calcium influx into the cell. These studies provide the first evidence that AVP modulates ANP production from cultured neurons. In the central nervous system, these two vasoactive neuropeptides might interact in part through the regulation of ANP production by AVP.
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PMID:Arginine vasopressin stimulates atrial natriuretic peptide gene expression and secretion from rat diencephalic neurons. 138 Apr 42

Physiological role and importance of calcium ion has been investigated based on the study of the mechanism of muscle contraction. Furthermore, calcium ion has been proved to have a wide variety of biological roles in hormonal secretion, cell proliferation and reproduction as well as in muscle contraction. In this lecture, I would like to show a method to measure intracellular calcium ion concentrations ([Ca2+]i) and to give a general information about the roles of calcium ion to induce various cell activities. Then I would like to talk about the changes in intracellular calcium concentration ([Ca2+]i) and their meaning in the field of reproductive physiology including uterine muscle contraction, pituitary LH secretion, and fertilization. 1) Uterine muscle contraction and calcium ion The function of calcium ion is most intensively investigated in muscle contraction. We show [Ca2+]i increase in cultured myometrial cells. This increase is inhibited by omission of extracellular calcium or addition of calcium channel blockers. These results support usefulness of Ca2+ channel blockers in treating threatened premature delivery. We also report the action of MgSO4 as an inhibitory agent of [Ca2+]i increase stimulated by oxytocin. 2) Pituitary gonadotropin secretion and calcium ion Pituitary LH secretion is regulated by gonadotropin releasing hormone (GnRH). GnRH induces rapid increases and then sustained releases of LH secretion. By the omission of extracellular calcium, or by addition of Ca2+ channel blockers, the sustained phase of LH secretion is abolished. GnRH also increase [Ca2+]i in a very similar manner to that of LH secretion. The [Ca2+]i increase is essential in LH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Roles of calcium ion in reproductive physiology]. 140 28

Studies were undertaken to evaluate the efficacy of the beta 2-adrenergic agonist ritodrine and the calcium channel blocker nifedipine, alone and in combination, for inhibition of contraction in isolated rat uterine strips. Both compounds produced a dose-dependent reduction of area under the curve. When contractions were produced by oxytocin, a 26% reduction was observed with 0.144mcg of ritodrine and a significant 68.1% decrease was produced with 1.44mcg of ritodrine. Contraction frequency (contractions per ten minutes) was not significantly affected. Prostaglandin F2 alpha-induced contractions were significantly inhibited 27.1% and 62.2% by 1.44mcg and 14.4mcg of ritodrine, respectively. Also, contraction frequency was significantly affected by both concentrations. Inhibition of area under the curve of oxytocin-induced contractions produced by nifedipine was 39.3% for 0.05mcg and 78.4% (P less than 0.05) for 0.50mcg. Contraction frequency was unaffected. Prostaglandin F2 alpha-induced contractions were significantly attenuated by 60% and 86% with nifedipine (0.50mcg and 5.02mcg, respectively); contraction frequency was significantly reduced from 15 to 2 contractions per ten minutes by 5.02mcg. Oxytocin-induced contraction was attenuated 39.8% by a combination of ritodrine 0.144mcg and nifedipine 0.05mcg; contraction frequency was unaffected. Area under the curve and contraction frequency of oxytocin-induced contractions were significantly decreased by a combination of ritodrine 0.144mcg and nifedipine 0.50mcg (89.8% reduction; decrease in frequency from 12 contractions in control to 4 contractions post-inhibitory agent). Significant attenuation of prostaglandin F2 alpha-induced contractions was produced by ritodrine 1.44mcg and nifedipine 0.50mcg. Area under the curve decreased by 73.2% and frequency was reduced from 13 to 8 contractions. A combination of ritodrine 1.44mcg and nifedipine 5.02mcg also produced significant decreases in area under the curve (85.3%) and frequency (13 contractions in control to 1 contraction after compounds were added). Because the mechanisms of action of these two agents are different, it is reasonable to suggest that they be used in combination to control premature labor. The results of this study suggest they may provide inhibition of contraction superior to either agent alone, and could therefore provide more effective inhibition and possibly reduce untoward side effects common to ritodrine therapy.
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PMID:Influence of a combination of ritodrine and nifedipine on the isolated rat uterus. 162 25

1. Jatrophone (JAT), a diterpene isolated from the plant Jatropha elliptica (1-300 microM), caused a concentration-dependent relaxation effect against acetylcholine (Ach)-oxytocin (Ot)- and KCl-induced uterine sustained contraction. The relative potency order was: Ach greater than Ot greater than KCl. 2. The relaxant effect of JAT was not modified by phorbol ester, forskolin, MIX, TMB-8 and W-7. The increase concentration of calcium (0.2-2 mM) in the medium did not reverse the inhibitory effect caused by JAT. 3. Pre-incubation of the preparations with JAT (16-32 microM) for 20 min, caused a concentration-dependent inhibition of KCl-induced contractile response. At 30 microM, JAT inhibited in an apparently non-competitive manner CaCl2-induced contraction in K+-depolarized preparations. High concentrations of JAT (100 microM) also caused a time-dependent relaxation in CaCl2-induced sustained uterine contraction (T1/2 = approx. 15 min). 4. JAT (30 microM) inhibited the dihydropyridine calcium channel agonist Bay K 8644-induced uterine contraction in an apparently non-competitive fashion, while verapamil (0.1 microM) caused an rightward displacement of Bay K 8644 contraction and marked inhibition of the maximal response.
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PMID:Evidence for the mechanism of the inhibitory action of jatrophone in the isolated rat uterine muscle. 168 18

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 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

Neurosecretory terminals (neurosecretosomes, NSS) were isolated from rat neurohypophyses. High [K+]o or veratridine stimulated secretion of vasopressin and oxytocin by up to approximately 100-fold. Stimulated secretion was dependent on calcium and temperature, and could be elicited from NSS maintained in culture for 4 days. After overnight culture of the NSS, secretion was still inhibited by calcium channel blockers (cobalt, dihydropyridines, omega-conotoxin, D 600) and kappa opiates (dynorphin and U50488). Ionomycin evoked dose- and calcium-dependent hormone release, with a Hill coefficient for calcium of 1.74. High [K+]o enhanced the 5 microM ionomycin-induced secretion, apparently through calcium entry rather than depolarization, as the increase in secretion was abolished by 100 microM D 600. During prolonged depolarization the hormone secretion peaked within 2 min, then declined to near basal levels. Depolarization for 25 min without calcium neither activated secretion nor prevented subsequent secretion on readdition of calcium, suggesting that the decline in secretion was not due to membrane depolarization. Indeed, the rates of decline in secretion were similar for different levels of depolarization (0.070 +/- 0.003 and 0.081 +/- 0.003 min-1 for 25 and 45 mM [K+]o, respectively). Four minutes after the onset of continuous depolarization (45 mM [K+]o) in the presence of calcium, the declining secretion was still dependent on voltage-activated calcium influx through channels sensitive to D 600 and nitrendipine. The results presented here suggest that the decline in secretion during prolonged depolarizing stimuli may be due to exhaustion, inactivation, or desensitization of a calcium-triggered event.
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PMID:Activation and inactivation of oxytocin and vasopressin release from isolated nerve endings (neurosecretosomes) of the rat neurohypophysis. 207

Uterine hyperactivity causing reduced local blood flow is quite prevalent among nulliparous women in their late teens. This pain called primary dysmenorrhea coincides with the onset of menstruation and stays a few hours to 1-2 days. The uterine agonist prostaglandin PGF2alpha and arginine vasopressin (VP) seem to be involved in dysmenorrhea. Pgf2alpha may induce pain by stimulating afferent nerve fibers. Generally common pain relievers treat dysmenorrhea, but in those instances when they do not, nonsteroid antiinflammatory drugs (NSAIDs) may do so (75% success rate). Yet NSAIDs may not be able to help because of the sizable time lag between ingestion and affecting pain. Moreover pain transpire very quickly and does not always last very long. Nevertheless clinical studies how promise for the NSAID ketoprofen. Plasma levels of ketoprofen reach their peak in 1 hour while it takes naproxen (the reference NSAID) about 2 hours to reach peak plasma levels. Oral contraceptives (OCs), especially those that are gestagen dominated, can also treat primary dysmenorrhea. OCs reduce the strong uterine contractions, blood flow, and sensitivity of the uterus to Pgf2alpha and VP. Calcium channel blocking agents and beta 2 adrenoceptor stimulating drugs may help when other treatments fail, but they have significant side effects. Moreover calcium channel blocking agents are not yet approved in Scandinavia. A double blind cross over comparative study with an intravenous oxytocin analogue shows good promise, but an oral preparation is not yet available. Secondary dysmenorrhea occurs most often in women 30 years old. A bodily condition, such as endometriosis or an IUD, is responsible for it. Many of these conditions stimulate the release of PGs so NSAIDs can generally relieve the pain. Ideally, to relieve suffering though, physicians should treat the condition.
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PMID:Modern treatment of dysmenorrhea. 209 35


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