Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of drugs which affect the movement of calcium on the contractions induced by 50 and 200 nM oxytocin in the isolated testicular capsule of the rat. The ED50 for oxytocin in this preparation was 188 (+/- 66 S.E.) nM and the maximal contraction induced by oxytocin was smaller than that obtained with 10 microM of the calcium ionophore, A23187. Lanthanum (10 mM), cobalt (2 mM), EGTA (3.5 and 5 nM, 30 s exposure) and a decrease in the calcium concentration of the medium reduced the oxytocin response. The response was completely abolished after prolonged incubation with EGTA (2 mM) in a calcium-free medium. The calcium blocking agents, nifedipine and flunarizine, and the agonist, Bay K 8644, did not modify the responses to oxytocin. Verapamil, at possibly non-specific doses (10 microM), reduced the contractions while diltiazem (0.1 mM), in a prazosin (10 microM)-resistant way, and nickel (0.1 mM) increased them. Both modifiers of intracellular calcium that were used namely TMB-8 (10 microM), in a calcium-free medium, and dantrolene sodium (10 and 30 microM), with and without calcium in the medium, decreased the oxytocin response. On the whole, it seems as if both intra- and extracellular calcium were involved in the contractile effect of oxytocin, although extracellular calcium does not seem to gain access to the cell through voltage-dependent calcium channels sensitive to selective calcium entry blockers.
 ...
PMID:Interactions between oxytocin- and calcium-modifying agents in the rat testicular capsule in vitro. 260 46

Prolactin has been shown to increase the activity of ornithine decarboxylase in a variety of mammalian tissues and in the pigeon crop sac. This study demonstrates a similar effect of ovine prolactin on ornithine decarboxylase activity in liver slices taken from larval tiger salamanders (Ambystoma tigrinum). An evaluation of potential mediators of prolactin action in liver slices revealed that the effect of the hormone on enzyme activity was not blocked by ouabain, an inhibitor of the sodium pump reported to block other actions of prolactin. Oxytocin, which inhibits prolactin actions in A. tigrinum, blocked the increase in ornithine decarboxylase activity induced by prolactin. Since previous results had implicated inositol phospholipid turnover in oxytocin action, the effects of the calcium ionophore, A 23187, and of synthetic diacylglycerol were examined. Both agents blocked the increase in enzyme activity when they were combined with prolactin treatment. Verapamil, a calcium channel blocker, had a prolactin-like effect on the activity of ornithine decarboxylase, and the combination of prolactin and verapamil produced a stimulation of the enzyme that was no greater than that observed with either the drug or prolactin alone, suggesting that both agents might be acting via a common cellular pathway. The tentative hypothesis that prolactin acts via a mechanism which lowers intracellular calcium is suggested.
 ...
PMID:Enhancement of ornithine decarboxylase activity in Ambystoma liver slices by ovine prolactin: an evaluation of possible mediators. 314 Dec 45

The tonic contractions which are extremely resistant to removal of the external Ca were investigated in the rat vas deferens and myometrium. Both the noradrenaline response in the vas deferens and the oxytocin response in the myometrium could be repeatedly produced without appreciable diminution in Ca-free solution for more than 24 hrs. On the other hand, the tissue Ca content decreased exponentially after Ca-removal with a half time of 130-180 min. When Ca was readmitted, no indication of the early transient contraction was observed in the subsequent response in Ca-free solution, but the response was reduced compared with the response before Ca readmission. Verapamil suppressed the response in the presence of Ca, while it had very weak inhibitory effect even at 10 microM. Calmodulin antagonists of phenothiazine derivatives had a strong inhibitory effect on Ca-induced contractions, whereas they had very weak effects on the receptor-mediated contraction in Ca-free solution. Another calmodulin antagonist, W-7 suppressed both Ca-induced contraction and the contractions independent of external Ca. HA-1004, a vasodilator which has a structure similar to W-7, reduced the receptor-mediated contraction in Ca-free solution without much effect on Ca-induced contractions. These results may suggest that the receptor-mediated contractions resistant to Ca-removal are caused by some process without a contribution of the Ca-calmodulin system.
 ...
PMID:Contraction of smooth muscle in Ca-free solution. 405 13

Calcium channel blockers verapamil (2, 10nM), diltiazem (11, 22nM), nifedipine (2.9, 14nM) and salbutamol (21, 42nM) produced concentration dependent inhibition of oxytocin induced contractions in non-pregnant rats. With verapamil and nifedipine the effect was more marked at both low and high doses. Verapamil (1,2nM), diltiazem (2.2, 11nM), nifedipine (1.4, 2.9nM) and salbutamol (2.1, 4.2nM) produced significant inhibitory effect on PGF2 alpha (0.3 microgram) induced phasic tension. However, basal tension was significantly reduced by salbutamol and nifedipine only.
 ...
PMID:Effect of calcium channel blockers and salbutamol on oxytocin and PGF2 alpha induced uterine contractions in rats. 827 Feb 83

To investigate the relationship between the oxytocin (OT) receptor (OTR) quantity and the contractile features systematically, we measured the mRNA expression levels of OTR and L-type Ca(2+) channel alpha(1C)-subunit (alpha(1C)) and examined the regulatory mechanisms of OT-induced phasic or tonic contractions of the longitudinal smooth muscles in mouse uteri. The mRNA expression of OTR in 19.0 G (19.0 days of gestation) was greater than those in nonpregnant phases, and that of alpha(1C) in estrus and 19.0 G was higher than in diestrus. OT-induced contractions sparsely occurred in diestrus. The OT-induced all-or-none-type phasic contractions at low concentrations were abolished by verapamil in both estrus and 19.0 G. OT-induced tonic contractions had similar pD(2) values in both estrus and 19.0 G. However, the magnitude in 19.0 G was much greater than that in estrus. The large tonic contractions also occurred in PGF(2alpha) receptor (FP) knockout mice in 19.0 G despite a small amount of OTR. Verapamil and Y-27632 partially inhibited the tonic contractions in 19.0 G. Cyclopiazonic acid-induced tonic contractions were reciprocally decreased with the increase in the OT-induced ones in 19.0 G. These results indicate that the phasic contractions are dependent on alpha(1C). The tonic contractions in 19.0 G are dependent on both Ca(2+) influxes via L-type Ca(2+) channels and store-operated Ca(2+) channels, and the force is augmented by the Rho signal pathway, which increases the Ca(2+) sensitivity. Thus the uterine contractions are mainly controlled by the modification of contractile signal machinery rather than simply by the OTR quantity.
 ...
PMID:Oxytocin-induced phasic and tonic contractions are modulated by the contractile machinery rather than the quantity of oxytocin receptor. 1714 56

The effects and plausible mechanism of action of Curcuma aeruginosa Roxb. (Zingiberaceae) rhizome chloroform and methanol extracts on the uterine contraction were investigated using isolated uterus strips from estrogen primed rats. The contractile responses were recorded isometrically with a Grass FT03 force transducer connected to a MacLab system. The experiments were carried out on both nonstimulated, agonist- and KCl-stimulated uteri. In the nonstimulated uterus, the two extracts (10-400 microg/ml) had no significant effect. In contrast, in the stimulated uterus, the chloroform and methanol extracts exerted concentration-dependent inhibition of the contractions induced by oxytocin (1 mU/ml), prostaglandin F2alpha (PGF2alpha, 0.5 microg/ml), ACh (3x10(-6) M) and KCl (40 mM) with the IC50 (inhibition of force) of 31.4, 58.59, 56.21 and 29.28 microg/ml; and 57.79, 69.3, 223.8 and 69.19 microg/ml, respectively. Verapamil, the reference L-type calcium channel blocker, exhibited a similar pattern of inhibition with the IC50 of 0.03, 0.25, 0.35 and 0.04 microg/ml. The IC50 of diclofenac against a PGF2alpha-induced contraction was 31.36 microg/ml. It is known that the contraction induced by agonists and KCl is mainly due to calcium influx through the voltage-gated L-type calcium channels opened indirectly or directly by agonist-receptor activation and KCl. Thus, it is speculated that the two plant extracts might inhibit uterine contraction by interrupting the influx of Ca2+ probably through voltage-gated L-type calcium channels. This possibility was further substantiated by the ability of the extracts to shift the CaCl2-contraction curves to the right. As the methanol extract also reduced the contraction of oxytocin in Ca2+-free EDTA solution; thus, it is suggested that part of its action may be involved with an intracellular mechanism. The effect of the two extracts did not involve the activation of beta2-adrenoceptors since their effects were unaffected by propranolol. Based on the inhibitory effect of the extracts on the oxytocin-induced contraction, it is concluded that the extracts might be useful as tocolytic agents for the prevention of preterm labor. Their effects on the inhibition of PGF2alpha-induced contractions also seem useful for the treatment of dysmenorrhea. There are reports by others that the plant rhizome contains beta-pinene and sesquiterpenes. In addition, there is evidence that these compounds possess spasmolytic effects in the rat intestine and uterus. Therefore, the uterine relaxant effect of the plant extracts could be due to beta-pinene and some sesquiterpene lactones contents. The methanol extract is less potent than the chloroform extract, and this might be due to the lower amount of terpene compounds or different compounds may involve in this action.
 ...
PMID:Uterine relaxant effects of Curcuma aeruginosa Roxb. rhizome extracts. 1902 35