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

Calcium antagonists are valuable pharmacological tools for the study of stimulussecretion and excitation-contraction coupling mechanisms. Two 2-substituted 3-dimethylamino-5,6-methylenedioxyindene hydrochlorides were tested for antagonism of the spasmogenic action of various agonists on isolated smooth muscle preparations. The 2-n-propyl and 2-n-butyl aminoindenes (5 X 10(-5) to 10(-4) M) blocked the spasmogenic action on the estrogen-treated rat uterus of prostaglandin E2 (10(-7) M), prostaglandin F2alpha tromethamine salt (10(-7) M), oxytocin (10(-3) U/ml), barium chloride (BaCl2-2H2O; 2.2 X 10(-4) M), acetylcholine chloride (10(-6) M) and ergonovine maleate (7.5 X 10(-4) M); they also blocked the contractile effect on the ileum of acetylcholine chloride (10(-6) M; rat) and histamine hydrochloride (10(-6) M; guinea pig). In further experiments on rat uterus using the agonists acetylcholine chloride (10(-6) M; which presumably acts by increasing influx of extracellular calcium into cells) and barium chloride (2.2 X 10(-4) M; which presumably contracts smooth muscle by releasing intracellular calcium), a progressive increase in extracellular calcium concentration (from 9 X 10(-4) to 7.2 X 10(-3) M CaCl2-2H2O) was paralleled by progressive reversal of the blockade produced by both 2-substituted aminoindene antagonists. In studies on the perfused bovine adrenal medulla, the 2-n-propyl aminoindene (10(-4) M) completely blocked the calcium-dependent catecholamine secretion evoked by 0.1 and 3.3 mM carbachol, without affecting the calcium-independent catecholamine secretion evoked by 33 mM acetaldehyde. These findings suggest that the aminoindene antagonists interfere with the action of calcium and that in smooth muscle the antagonism is at an intracellular site involved in excitation-contraction coupling.
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PMID:Pharmacological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes. 85 Jan 35

We have studied the effect of nonsteroidal antiestrogens on rat uterine contractions induced by oxytocin (8 nmol/l), methacholine (10 mumol/l), prostaglandin F2 alpha (1 mumol/l), KCl (60 mmol/l) and CaCl2 (6 mmol/l). In a concentration-dependent way, the antiestrogens tamoxifen, clomiphene, nafoxidine and ethamoxytriphetol inhibited the amplitude and frequency of the oxytocin-induced contractions and the contraction produced by CaCl2. At a concentration of 30 mumol/l the four drugs inhibited the contractions induced by methacholine and prostaglandin F2 alpha. They also relaxed the tonic contraction to KCl in a concentration-dependent way. This action was partially counteracted by CaCl2 (0.1-10 mmol/l). Bay k 8644 (0.3 nmol/l to 3 mumol/l) only partially reversed the inhibition by ethamoxytriphetol (0.1 mmol/l) of CaCl2 (6 mmol/l)-induced contractions. The steroidal antiestrogen, ICI 164,384, which lacks agonist activity, had an inhibitory effect (44 +/- 4%, n = 7) on KCl-induced contractions only at a concentration of 0.1 mmol/l. However, the quaternary analogue of tamoxifen (tamoxifen ethyl bromide) produced 86 +/- 3% relaxation of the KCl-induced contracture (IC50 1.52 +/- 0.1 mumol/l, n = 10) and this effect was counteracted by addition of CaCl2. Taken together the results indicate that the inhibitory effects of nonsteroidal antiestrogens on rat uterine contractions could be mediated by an action to block Ca2+ entry through an agonist action on extracellular estrogen receptors.
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PMID:Effects of nonsteroidal antiestrogens in the in vitro rat uterus. 148 55

The influence of testosterone on voltage-dependent calcium channels was observed indirectly in Ca(2+)-free depolarizing K+ solution (DKS). In this solution cumulative dose response curves to CaCl2 by increasing the Ca2+ concentration in logarithmic increments (10(-5)-10(-3) mol.1(-1] were obtained. The maximal response to CaCl2 and pD2 value were evaluated in these experiments. Decrease of guinea pig uterus contractility to CaCl2 after testosterone (T) administration was found. The pD2 value was unchanged. The possible influence of testosterone on calcium ion release from intracellular storage was investigated in Ca(2+)-free Tyrode's solution (TS). The reactivity of uterus to oxytocin (OT) at a dose of 2.10(-4) mol.1(-1) was decreased after testosterone administration. According to these results an important role of testosterone on calcium ion transport in myometrial cells could be suggested.
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PMID:The possible influence of testosterone on calcium ion transport (investigated) in guinea pig uterus. 165 14

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

1. The effects of phenidone (P, 10(-4)-10(-3) M), sodium diclofenac (D, 10(-5)-10(-4) M) and ethacrynic acid (E, 10(-5)-10(-4) M), proposed as inhibitors of eicosanoid synthesis, on the contractions of rat uterus induced by several agonists have been studied. 2. P, D and E inhibit the motility induced by oxytocin (4 mU/ml) (IC50: 4.62 x 10(-4), 2.55 x 10(-4) and 2.98 x 10(-5) M, respectively). 3. P (10(-3) M), D (10(-4) M) and E (10(-4) M) also inhibit the contraction induced by methacholine (10(-5) M), prostaglandin F2a (10(-6) M) and CaCl2 (6 mM), and relaxed, in a dose-dependent way, the tonic component of contraction to KCl (60 mM) (IC50: 5.81 x 10(-4), 6.67 x 10(-5) and 7.55 x 10(-5) M, respectively). 4. The CaCl2 (0.1-10 mM) reverted the relaxation of KCl contraction produced by P, but not by D or E. None of the inhibitions on CaCl2 (6 mM) are reverted by Bay K 8644. 5. D and E also relaxed the tonic contraction to vanadate (10(-4) M) in uterus incubated in calcium free solution P, enhances the vanadate-induced contractions.
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PMID:Mechanisms involved in the effects of phenidone, diclofenac and ethacrynic acid in rat uterus in vitro. 171 10

1. The effects of 4 inhibitors of eicosanoid synthesis (ESIs)--mepacrine (MEP, 10(-5) - 3 x 10(-4) M), nordihydroguaiaretic acid (NDHGA, 10(-6) - 2 x 10(-5) M), indomethacin (IND, 2 x 10(-6) M and 2 x 10(-5) M) and imidazole (IMI, 10(-5) M and 10(-4) M)--on the motility induced by oxytocin (OT, 0.5 and 4 mU/ml) in uterus of rats in natural oestrus and of ovariectomized rats have been studied. 2. MEP, NDHGA and IND, but not IMI, inhibited the motility induced by both concentrations of OT in natural oestrus. Ovariectomy enhanced the effects of all ESIs, except the one of MEP. 3. MEP and NDHGA, but not IND or IMI, inhibited the contractions induced by methacholine (10(-5) M) and prostaglandin F2a (10(-6) M) and relaxed in a dose-dependent way the tonic component of the contractile response to KCl 60 mM (DI50: 6.14 +/- 0.38 and 1.38 +/- 0.29 x 10(-5) M, respectively). 4. CaCl2 (0.1-10 mM) reverted the relaxation of KCl contractions produced by MEP but not by NDHGA.
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PMID:Effects of inhibitors of eicosanoid synthesis in the uterus of ovariectomized rats and rats in natural oestrus: relation with calcium. 229 92

Intracellular free calcium concentrations were measured directly in rat myometrial cells loaded with fura-2. The basal concentrations of calcium were 148 +/- 5.0 and 137 +/- 3.7 nM in the presence and absence of 1 mM extracellular calcium, respectively. Oxytocin, carbachol, and norepinephrine rapidly and transiently increased intracellular free calcium, with half-maximal effects at 0.19, 9.9, and 5.3 microM, respectively. The maximal effects of these agents were reduced by 57%, 32%, and 36%, respectively, when the extracellular calcium was replaced by 2 mM EGTA. Pretreatment with pertussis toxin partially (47-57%) inhibited the contractant-induced increase in intracellular free calcium in the presence of 1 mM extracellular CaCl2 and produced an even greater inhibition (76-98%) in the absence of extracellular calcium. Pretreatment with D600 (30 microM) or amiloride (50 microM) and reduction of extracellular sodium did not affect the oxytocin-induced calcium increase. However, adenosine and the A2-receptor agonist N-ethylcarboxamidoadenosine did attenuate the effect of oxytocin in a dose-dependent manner. These data represent the first direct evidence that oxytocin, carbachol, and norepinephrine increase the intracellular free calcium concentration in the rat myometrium. The data suggest that contractants mobilize calcium from both extracellular and intracellular sources, the latter involving a pertussis toxin-sensitive mechanism.
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PMID:Changes in intracellular free calcium in isolated myometrial cells: role of extracellular and intracellular calcium and possible involvement of guanine nucleotide-sensitive proteins. 249 4

Nafazatrom inhibits, in a dose-dependent way, the amplitude and frequency of the rhythmic contractions induced by oxytocin (4 mU/ml), as well as the methacholine (10(-5) M)- and CaCl2 (10 mM)-induced contractions, and the phasic response to KCl (60 mM); similarly, it inhibits the tonic contraction induced by KCl (60 mM) and oxytocin (10 mU/ml). A single concentration of nafazatrom (10(-4) M) also inhibits the uterine contractions caused by carbachol (10(-4) M) and prostaglandin F2 alpha (10(-6) M). CaCl2 (0.1-10 mM) only partially reverses the inhibition produced by nafazatrom on the KCl-induced tonic contractions. Bay K 8644 (3 x 10(-10)-3 x 10(-7) M) reverses the inhibition by 10(-4) M but not by 3 x 10(-4) M of nafazatrom on the CaCl2-induced contractions. Nafazatrom also inhibits, in a dose-dependent way, the calmodulin-dependent phosphodiesterase activity. Our results would suggest that, independently of its 5-lipoxygenase blocking activity, nafazatrom inhibits the contractions of the rat uterus by inhibiting the calmodulin activity and, presumably, by reducing the influx of extracellular calcium and/or the mobilization of intracellular calcium.
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PMID:Mechanism of nafazatrom-induced inhibition of rat uterus contractions in vitro. 256 Mar 65

The influence of thyroid dysfunction on rat myometrial responsiveness to oxytocin, acetylcholine, CaCl2 and BaCl2 was assessed in uterine strips from pregnant and nonpregnant rats. In preparations obtained from hypothyroid nonpregnant rats, oxytocin and acetylcholine concentration-response curves were significantly displaced to the left, whereas myometrial strips from hyperthyroid nonpregnant rats were only supersensitive to acetylcholine. In relation to the pregnant state, T3 treatment caused an increased myometrial sensitivity to both oxytocin and acetylcholine. In this condition, concentration-response curves for oxytocin did not differ from nonpregnant control animals, whereas acetylcholine was about 300-fold more potent at the ED50 levels compared with those in nonpregnant animals. Either in pregnant or nonpregnant state, maximal responses and ED50 to BaCl2 did not differ. In addition, thyroid dysfunction did not modify the pattern of CaCl2-induced contractions in isolated myometrial strips from pregnant rats. This data extended to the myometrium, previous evidence in the literature indicating that thyroid dysfunction may affect uterine responsiveness to agonists.
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PMID:Effect of induced thyroid dysfunction upon uterine responsiveness in strips from pregnant and nonpregnant rats. 275 63

Vasopressin and oxytocin immunoreactivity (AVP-IR, OT-IR) have been detected in the trigeminal and dorsal root ganglia (TG, DRG) of the rat. We have investigated whether AVP or OT have any neurotransmitter role in these tissues by measuring the effects of the peptides on levels of intracellular second messengers. AVP and OT at concentrations up to 3 x 10(-6) M have no effect on the accumulation of cAMP. However, in tissue prelabelled with 3H-inositol, and in the presence of 10 mM Li+, AVP and OT cause an increase in the accumulation of inositol phosphates (IP), in a dose-dependent manner. AVP causes a maximum stimulation of 1.7 fold of control in TG, (p less than 0.01) and of 2.5 fold in DRG (p less than 0.01) at a concentration of 3 x 10(-7) M. OT causes a maximum stimulation of 1.3 fold of control in TG, (p less than 0.01), and of 1.75 fold of control in DRG, at a concentration of 3 x 10(-6) M. The stimulation of IP turnover by AVP in both tissues is inhibited by the specific V1-antagonist, (CH2)5Tyr(Me)AVP, at a concentration of 2 x 10(-5) M. The V2-agonist, DDAVP, has no effect on IP accumulation in either tissue at concentrations up to 3 x 10(-6) M. The response to exogenous AVP is still present in ganglia incubated in media without added CaCl2. We conclude that the rat TG and DRG contain receptors for AVP, and that these receptors have characteristics associated with the V1 subtype.
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PMID:Vasopressin-induced turnover of phosphatidylinositol in the sensory nervous system of the rat. 282 10


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