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

Endothelins 1, 2 and 3 (ET-1, ET-2 and ET-3; 1-30 nM) caused long-lasting concentration-dependent tonic contractions of uterine strips from non-pregnant rats. The potency of ET-1 (EC50 7 nM) was similar to that of angiotensin II (AII) and greater than that of ET-2 or ET-3 (EC50S greater than or equal to 10 nM), bradykinin, Bay K 8644, oxytocin (OT), 5-hydroxytryptamine, prostaglandin F2 alpha (PGF2 alpha) or acetylcholine. Strips from 21-day pregnant rats were 2- to 3-fold more sensitive to ET-1, AII, OT and PGF2 alpha and 200-fold more sensitive to Bay K 8644 than non-pregnant preparations. The development of tonic responses to ET-1 (30 nM) and of phasic-rhythmic ones to Bay K 8644 (300 nM) was fully prevented in strips from non-pregnant rats bathed in Ca2(+)-free medium, but stepwise reintroduction of Ca2+ (0.03-3 mM) to the solution allowed the manifestation of contractions in response to both agonists. Responses to ET-1 required less Ca2+ than those to Bay K 8644. Strips challenged with ET-1 while in Ca2(+)-free medium developed greater contractions upon reintroduction of Ca2+ than preparations stimulated with the peptide in normal medium. The reverse occurred with Bay K 8644-induced contractions. Nicardipine (10 nM) abolished the responses of strips from non-pregnant rats to Bay K 8644 (300 nM), but only attenuated ET-1-induced (30 nM) contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of endothelins, Bay K 8644 and other oxytocics in non-pregnant and late pregnant rat isolated uterus. 171 Jan 86

The mechanical properties of the longitudinal and circular muscle tissues of the human umbilical vein and the effects of nicardipine were investigated. Spontaneous contractions were observed in the isometric condition. When high concentrations of potassium (118mM-K+), oxytocin and serotonin were applied, these substances evoked contractions. Oxytocin (10(-4)-10(-2) U/ml) enhanced the spontaneous contractions. Serotonin produced contractions at 10(-9)-10(-4) M in both the longitudinal and circular muscle strips. When nicardipine (10(-5) M) was applied, contractions induced by 118mM-K+ were completely inhibited, but contractions induced by serotonin could not be completely abolished, i.e., tonic contractions ceased but small phasic contractions continued. Nicardipine (10(-8) M) did not inhibit the amplitude and frequency of spontaneous contractions, but decreased the basal tonus. These results suggested that nicardipine might improve feto-placental blood flow while decreasing the spontaneous basal tonus.
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PMID:Effect of vasoconstrictor and vasodilator on isolated human umbilical vein. 191 87

Increasing concentrations of nicardipine were found to inhibit various types of muscular activation (electrical stimulation, acetylcholine, oxytocin, potassium chloride), as well as the spontaneous rhythmic activity of the isolated rat uterus. The degree of the inhibitory effect of nicardipine depends on the type of activation. Nicardipine showed an exceptionally high efficacy in inhibiting contractions induced by electrical stimulation and of spontaneous rhythmic activity. For inhibition of these contractions, even femtomolar concentrations of nicardipine were sufficient. The relaxant effect of nicardipine depends on the concentration of extracellular calcium and the temperature of the medium. Nicardipine shows high selectivity for the uterine smooth muscle because even in very high concentrations it exerts an insignificant relaxation of the other isolated smooth muscles (oesophagus, bladder, colon descendens) as well as of the isolated intercostal muscle of the rat. Our experiments indicate that nicardipine might have a role in the therapy of premature delivery and abortion because of its great selectivity for the uterine smooth muscle. Nicardipine causes a stronger inhibition of the tonic than of the phasic component of contraction induced by potassium chloride and oxytocin. These findings suggest that potassium chloride and oxytocin act through various populations of calcium channels.
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PMID:Effect of nicardipine on the isolated uterus and other smooth muscles of the rat. 324 44

A new potent vasodilator, nicardipine hydrochloride inhibited oxytocin-induced contraction of rat uterus dose-dependently with an increase in the intracellular cyclic AMP level at the onset of relaxation. Dibutyryl cyclic AMP and papaverine, an inhibitor of cyclic AMP phosphodiesterase (PDEase), also inhibited the contraction. Nicardipine inhibited competitively PDEase in homogenates of rat uterus which exhibited apparently two Km values for cyclic AMP (3.6 micro M and 67.3 micro M) with the Ki of 5.3 micro M and 13.2 micro M, respectively, but had no effect on adenylate cyclase. Nicardipine enhanced calcium uptake by rat uterine microsomes, at concentrations which inhibited oxytocin-induced contraction in the same manner as cyclic AMP. The maximal stimulation by nicardipine of the microsomal calcium uptake was identical substantially to that by cyclic AMP, and both were not additive. Cyclic AMP was also accumulated during the uptake reaction in the presence of nicardipine. On the contrary, neither myosin ATPase nor microsomal Ca2+-dependent ATPase was inhibited directly by nicardipine. These results suggest that the inhibition of oxytocin-induced contraction of rat uterus by nicardipine may be due to an enhancement of microsomal calcium uptake, mediated by cyclic AMP accumulated through the inhibition of PDEase.
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PMID:A possible mechanism for relaxation of rat uterine smooth muscle by nicardipine hydrochloride (YC-93), a new potent vasodilator. 627 30

Nicardipine, a calcium antagonist, suspended the spontaneous activity of the excised rabbit uterus at a concentration of 1 microgram/ml and abolished the electrical excitability at a concentration of 10 microgram/ml. In situ, single doses of 100 and 500 microgram reversibly suspended the spontaneous activity of the postpartum rat uterus (n = 22) for 34 +/- 6 minutes and 94 +/- 9 minutes, respectively. Furthermore, the intrauterine administration of prostaglandin F2 alpha or oxytocin failed to elevate intrauterine pressure in the postpartum rats (n = 18) injected with an average dose of 207 +/- 28 microgram of nicardipine. The administration of nicardipine to the rats (n = 19) immediately after the spontaneous delivery of the first fetus arrested labor, and the delivery of the subsequent fetuses was markedly delayed as compared to the control rats (n = 20). Similarly, when premature labor was induced by ovariectomy (OVX) on day 16, OVX control rats (n = 6) receiving 5 microgram/day of estradiol delivered 82% of the fetuses within 48 hours of OVX, whereas the rats treated with nicardipine (n = 7) delivered only 4% of the fetuses. All fetuses were delivered alive and were normal. Since the estradiol, progesterone, and prostaglandin profiles in the heart plasma, uterine vein plasma, and uterine tissue of the control and experimental rats were similar, the prevention of premature labor resulted from the antagonistic action of nicardipine to calcium.
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PMID:Deactivation of the uterus during normal and premature labor by the calcium antagonist nicardipine. 705 50

Calcium channel blockers are widely used as first-line tocolytic, but prescribed off-label for this indication. The primary objective of this review is to evaluate the efficiency and safety of calcium channel blockers compared to placebo and to all tocolytic agents used. This review concerns the randomized trials, comparative studies and meta-analyzes of randomized trials on the subject. Nifedipine is superior to placebo in reducing the risk of delivery within 48 hours (RR=0.3; 95 % CI [0.21-0.43]), but induces more maternal side effects (RR=3.8; 95 % CI [1.02-16.92]). The effectiveness of nifedipine is greater than that of betamimetics to prolong pregnancy beyond 48 hours (OR=1.52; 95 % CI [1.03-2.24]), and up to 34 weeks (OR=1.87; 95 % CI [1.11-3.15]), with a lower incidence of adverse events requiring discontinuation of treatment in case of use of nifedipine (RR=0.22; 95 % CI [0.10-0.48]), but no significant difference in neonatal mortality. Efficacy of nifedipine is similar to that of oxytocin antagonists to prolong pregnancy beyond 48 hours (RR=0.92; 95 % CI [0.37-2.30]), but causes more mild maternal adverse events (RR=2.61, 95 % CI [1.43-4.74]). Nicardipine is not evaluated as nifedipine as a tocolytic treatment. It appears as effective as salbutamol and appears to have fewer maternal side effects than IV salbutamol.
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PMID:[Efficiency and tolerance of calcium channel blockers as first-line tocolysis]. 2572 82