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

Myometrial tissue was obtained from non-pregnant women subjected to hysterectomy because of various gynaecological disorders, and from women undergoing caesarean section. Strip preparations were dissected and isometric tension was recorded. Nifedipine (2.9 X 10(-8)--2.9 X 10(-6)M) inhibited spontaneous contractile activity, mainly by reducing the amplitude of contraction in both non-pregnant and pregnant myometrium. The drug also inhibited potassium induced contractions in a concentration dependent manner. This effect seemed to be more pronounced in pregnant than in non-pregnant tissue. In preparations of pregnant human myometrium, normally polarized or potassium depolarized, oxytocin induced a contractile activity that was effectively inhibited by nifedipine. Nifedipine also relaxed contractions induced by vasopressin in isolated non-pregnant myometrium. It is concluded that the relaxant effect of nifedipine on isolated pregnant and non-pregnant human myometrium can be explained by inhibition of calcium influx. The results thus support the view, that calcium influx is an important step in the initiation of contractile activity in human uterine smooth muscle.
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PMID:Relaxant effects of nifedipine on isolated, human myometrium. 49 17

An assessment was made of the potencies of nifedipine, gallopamil, diltiazem, cinnarizine and salbutamol as inhibitors of tension development by the uterus and cardiovascular tissues from the term pregnant rat. The rank order of potency was nifedipine greater than gallopamil greater than diltiazem for those preparations on which these compounds were potent, viz. spontaneous and oxytocin-induced tension development of the uterus, spontaneous tension development of hepatic portal vein, potassium chloride (KCl)-induced pressure rises of perfused mesenteric bed and electrically-stimulated (0.5 Hz) ventricular muscle. The rank order of potency of nifedipine, gallopamil and diltiazem was different for those preparations on which they exhibited low potency, viz. noradrenaline-induced pressure rises of perfused mesenteric bed and tension development of aorta. Gallopamil and diltiazem, but not nifedipine, were more potent against tension development by ventricular muscle stimulated at 2.5 Hz than at 0.5 Hz, suggesting that nifedipine interacts at a different site from the other compounds. Cinnarizine was less potent than the other calcium antagonists on the uterus and portal vein, was the second most potent compound against KCl-induced pressure rises of the mesenteric bed and was equipotent against responses to noradrenaline and KCl of the mesenteric bed (unlike the other compounds). This suggests that the site of action of cinnarizine differs from that of the other calcium antagonists. Nifedipine, gallopamil and diltiazem, like salbutamol, exhibited selectivity for inhibition of tension development by the uterus relative to the cardiovascular tissues.
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PMID:A comparison of several calcium antagonists on uterine, vascular and cardiac muscles from the rat. 402 68

Both verapamil and nifedipine were found to inhibit various types of activation of the isolated rat uterus, as for example: tonic and phasic components of contraction produced by KC1 and by oxytocin, phasic components of contraction produced by electrical stimulation and phasic spontaneous rhythmic activity. Presumably, verapamil and nifedipine affect a common pathway in calcium metabolism in all three types of muscle activation. Both verapamil and nifedipine inhibited more the contractile responses to high concentrations of KC1 than the responses to oxytocin, indicating the possibility of KCI and oxytocin acting through different calcium channels. Nifedipine inhibited more the tonic than phasic components of contractions produced by both KCI and oxytocin. It is assumed that two different calcium channels might be implicated in two components of contractions produced by KCI and oxytocin. Phasic components of contraction produced by KCI and by electrical stimulation were almost completely restored by increasing the concentration of calcium in the medium, whereas tonic components were restored only to about 50%.
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PMID:The effect of calcium-channel-blocking agents on the various types of smooth muscle activation of the isolated rat uterus. 649 4

In order to get additional information on spontaneous and drug-induced uterine activity in the early postpartum period, intrauterine pressure was registered by the microtransducer technique in 19 patients. The effects of the calcium entry blocker nifedipine were also tested. Myometrial activity was induced by infusion of oxytocin (10 patients) or prostaglandin F 2 alpha (nine patients). Both hormones increased myometrial activity, with slightly different patterns of contractility. Nifedipine effectively reduced contractions induced by both drugs. The microtransducer technique seems to be a convenient and safe method for studying the effects of drugs and hormones on uterine activity post partum. Furthermore, nifedipine administered orally is a potent inhibitor of drug-induced myometrial activity in the early postpartum period.
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PMID:Effects of nifedipine on oxytocin- and prostaglandin F2 alpha -induced activity in the postpartum uterus. 695 5

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

The effects of ouabain and K(+)-free solution were studied in estrogen-primed rat uterine strips under resting tone or repeatedly stimulated with KCl, acetylcholine or oxytocin applied for 20 minutes at 60 minute intervals. These effects were compared with those of the K+ channel opener cromakalim. In preparations under resting tone, ouabain (0.1 mM and 0.3 mM) induced rhythmic contractions which disappeared after 20-30 minutes whereas at a higher concentration (1 mM) it evoked a rapid, phasic response followed by a small tonic contraction. Exposure of the strip to a K(+)-free solution induced either rhythmic waves, which ceased after 8-10 minutes, or a single phasic contraction which was followed by a small and slow increase in the resting tone (54 +/- 10 mg after 180 min exposure). Nifedipine (0.3 microM) abolished the rhythmic or phasic component of these responses but failed to modify the late small tonic contraction induced by ouabain 1 mM or by K(+)-free solution. Ouabain (0.1-1 mM) or K(+)-free-evoked responses disappeared after short (4 min) or prolonged (60 min) exposure to a Ca(2+)-free, 3 mM EGTA-containing solution. Cromakalim (10 nM-0.1 mM) did not induce any variation in the resting tone either in the presence or in the absence of Ca2+ in the medium. In strips repeatedly stimulated with acetylcholine (0.1 mM) or oxytocin (1 microM), ouabain (0.3 mM), K(+)-free-solution and cromakalim (10 microM) reduced the amplitude of the initial, phasic response and progressively decreased the oscillatory component of the response to these agonists. Conversely, the successive responses evoked by KCl 60 mM in similar experimental conditions were not affected by ouabain or cromakalim. Ouabain (0.3 mM), K(+)-free solution and cromakalim (10 microM) decreased the Ca(2+)-independent, maintained contractions induced by acetylcholine or oxytocin after prolonged exposure to a Ca(2+)-free, EGTA-containing medium. These inhibitory effects were partially or completely reversed in the presence of the non-selective potassium channel blocker tetraethylammonium (10 mM) or in a Ca(2+)-free solution containing 60 mM K+. In conclusion, these results suggest that the response induced by ouabain or K(+)-free solution in estrogen-primed rat myometrium involves Ca2+ influx through potential-operated calcium channels but not Ca2+ release from intracellular stores. In addition, our results show that prolonged exposure to ouabain or K(+)-free medium decreases membrane receptor-mediated responses in rat uterus. This inhibitory effect seems to be the result, at least in part, of a decrease in the cytosolic level of K+, due to the inhibition of the electrogenic Na+ pump.
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PMID:Effect of inhibition of the electrogenic Na+/K+ pump on the mechanical activity in the rat uterus. 890 Apr 99

Mammary myoepithelial cells were isolated and cultured to characterize their properties. The intracellular calcium concentration (Cai2+) was measured using the ratio of fura-2 fluorescence at 340 nm to that at 360 nm (F340/F360), and the contraction was simultaneously monitored by the change of fluorescence intensity at 360 nm (F360). Cultured myoepithelial cells retained their contractile machinery as in the intact tissue. NBD-phallacidin fluorescence, which marks F-actin, and electron microscopy showed abundant bundles of microfilaments in the cytoplasm. Oxytocin (> 0.1 nM) induced an increase in Cai2+ and contraction. The amplitude and time course of the Cai2+ increase were not markedly affected in the Ca2+-free solution. Nifedipine (10 microM) did not affect the response to oxytocin. ATP (>1 microM) induced an increase in Cai2+ and contraction. The response to ATP was not affected by Ca2+ removal, but was suppressed by suramin (100 microM), an antagonist of P2-purinergic receptors. The order of potency of nucleotides to increase Cai2+ was ATP = ADP > UTP > UDP. These findings indicate the presence of P2-purinergic receptors in mammary myoepithelial cells. The results suggest that stimulant-induced Cai2+ increases and contractions are due to release of Ca2+ from intracellular stores in these cells. In addition to the hormonal action of oxytocin, extracellular nucleotides may function as paracrine agents to contract myoepithelial cells in the mammary gland.
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PMID:Involvement of P2-purinergic receptors in intracellular Ca2+ responses and the contraction of mammary myoepithelial cells. 935 97

The aim of the present study was to investigate the mechanisms involved in the contraction evoked by iso-osmotic high K+ solutions in the estrogen-primed rat uterus. In Ca2+-containing solution, iso-osmotic addition of KCl (30, 60 or 90 mM K+) induced a rapid, phasic contraction followed by a prolonged sustained plateau (tonic component) of smaller amplitude. The KCl (60 mM)-induced contraction was unaffected by tetrodotoxin (3 microM), omega-conotoxin MVIIC (1 microM), GF 109203X (1 microM) or calphostin C (3 microM) but was markedly reduced by tissue treatment with neomycin (1 mM), mepacrine (10 microM) or U-73122 (10 microM). Nifedipine (0.01-0.1 microM) was significantly more effective as an inhibitor of the tonic component than of the phasic component. After 60 min incubation in Ca2+-free solution containing 3 mM EGTA, iso-osmotic KCl did not cause any increase in tension but potentiated contractions evoked by oxytocin (1 microM), sodium orthovanadate (160 micrM) or okadaic acid (20 microM) in these experimental conditions. In freshly dispersed myometrial cells maintained in Ca2+-containing solution and loaded with indo 1, iso-osmotic KCl (60 mM) caused a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i). In cells superfused for 60 min in Ca2+-free solution containing EGTA (1 mM), KCl did not increase [Ca2+]i. In Ca2+-containing solution, KCl (60 mM) produced a 76.0 +/- 16.2% increase in total [3H]inositol phosphates above basal levels and increased the intracellular levels of free arachidonic acid. These results suggest that, in the estrogen-primed rat uterus, iso-osmotic high K+ solutions, in addition to their well known effect on Ca2+ influx, activate other cellular processes leading to an increase in the Ca2+ sensitivity of the contractile machinery by a mechanism independent of extracellular Ca2+.
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PMID:Cellular mechanisms involved in iso-osmotic high K+ solutions-induced contraction of the estrogen-primed rat myometrium. 1089 87

The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as "pennyroyal" or "poejo" that is used in folk medicine as an abortifaceant, were assessed on the isolated rat myometrium. Myometrial strips were stimulated with 10 nM oxytocin or 10 microM PGF (2alpha). EOMP (10 - 300 microg/mL) concentration-dependently and reversibly inhibited the amplitude of oscillatory contractions, being approximately 3-fold more active against contractions stimulated by oxytocin than those by PGF (2alpha) (IC (50) values of 45.7 +/- 5.6 microg/mL and 160.9 +/- 5.9 microg/mL , respectively), although the maximal inhibitory effect occurred at the same concentration (300 microg/mL ) in both cases. This action was shared by pulegone (30 - 300 microM), the principal component of the essential oil (IC (50) values of 21.8 +/- 2.1 microg/mL and 12.7 +/- 4.6 microg/mL , respectively). Nifedipine (30 nM - 30 microM) also abolished agonist-stimulated contractions, and was approximately twice and 12 times as potent as EOMP in inhibiting oxytocin- and prostaglandin F (2alpha) (PGF (2alpha))-stimulated contractions, respectively. In conclusion, our results show that the essential oil of the abortifaceant plant Mentha pulegium exerts an inhibitory effect on the contractile activity of the isolated rat myometrium. This oil shares a common effect with the voltage-dependent calcium channel (VDCC) blocker nifedipine, although ostensibly acting via a different mechanism. It thus appears that EOMP and pulegone do not exert direct toxic effects on the myometrium per se that would cause abortion, and other possibilities such as systemic metabolism of plant constituents may rather underlie the abusive use of Mentha pulegium in popular medicine.
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PMID:Inhibitory effects of the essential oil of Mentha pulegium on the isolated rat myometrium. 1577 May 40

Orexin A and B are neuropeptides implicated in the regulation of sleep/wakefulness and energy homeostasis. The regulatory mechanism of the activity of orexin neurons is not precisely understood. Using transgenic mice in which orexin neurons specifically express yellow cameleon 2.1, we screened for factors that affect the activity of orexin neurons (a total of 21 peptides and six other factors were examined) and found that a sulfated octapeptide form of cholecystokinin (CCK-8S), neurotensin, oxytocin, and vasopressin activate orexin neurons. The mechanisms that underlie CCK-8S-induced activation of orexin neurons were studied by both calcium imaging and slice patch-clamp recording. CCK-8S induced inward current in the orexin neurons. The CCKA receptor antagonist lorglumide inhibited CCK-8S-induced activation of orexin neurons, whereas the CCKB receptor agonists CCK-4 (a tetrapeptide form of cholecystokinin) and nonsulfated CCK-8 had little effect. The CCK-8S-induced increase in intracellular calcium concentration was eliminated by removing extracellular calcium but not by an addition of thapsigargin. Nifedipine, omega-conotoxin, omega-agatoxin, 4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride, and SNX-482 had little effect, but La3+, Gd3+, and 2-aminoethoxydiphenylborate inhibited CCK-8S-induced calcium influx. Additionally, the CCK-8S-induced inward current was dramatically enhanced in the calcium-free solution and was inhibited by the cation channel blocker SKF96365, suggesting an involvement of extracellular calcium-sensitive cation channels. CCK-8S did not induce an increase in intracellular calcium concentration when membrane potential was clamped at -60 mV, suggesting that the calcium increase is induced by depolarization. The evidence presented here expands our understanding of the regulation of orexin neurons and the physiological role of CCK in the CNS.
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PMID:Cholecystokinin activates orexin/hypocretin neurons through the cholecystokinin A receptor. 1609 97


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