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

The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium.
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PMID:Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs. 50 84

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

The effects of oxytocin, a uterotonic polypeptide hormone, on the voltage-dependent slow calcium, fast sodium, and potassium channel currents were studied using whole-cell voltage clamp of freshly isolated cells from late pregnant (18-21 day) rat myometrium. The calcium current was rapidly inhibited by oxytocin (about 25% inhibition at 20 nM) in a dose-dependent manner, and this inhibitory effect was completely reversible by washout. However, inhibition was not observed when barium was used as the charge carrier. Sodium current and potassium current were not modified by oxytocin, thus sodium and potassium currents may not play important roles in oxytocin-induced augmentation of uterine contraction. It is concluded that oxytocin stimulates uterine contraction by mechanisms other than augmentation of the voltage-dependent calcium current, e.g., by release of Ca from sarcoplasmic reticulum (by inositol triphosphate) or by activation of a receptor-operated Ca channel. The inhibition of the slow calcium current may be induced by the elevation of [Ca]i.
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PMID:Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells. 128 86

1. The mechanism of action of oxytocin on vagal neurones of the rat was studied using single-electrode voltage-clamp recordings from brainstem slices. The ionic basis of the oxytocin-induced current was examined by changing the composition of the perfusion solution and by making use of channel blockers. 2. In neurones clamped at or near their resting potential, oxytocin generated a sustained, TTX-insensitive inward current whose peak amplitude was concentration related. This current was detectable at 10 nM, was half-maximal at about 100 nM and was maximal at micromolar concentrations of peptide. 3. The oxytocin current was inward over membrane potentials ranging from -110 to -20 mV and was voltage dependent, since it increased in magnitude as the membrane was depolarized from the resting potential toward less negative potentials. 4. Partial replacement of extracellular sodium by equimolar N-methyl-D-glucamine reversibly attenuated or suppressed the oxytocin current. By contrast, substituting part of extracellular chloride or blocking calcium currents did not modify it. Increasing the transmembrane potassium gradient was also without effect and none of the potassium channel blockers TEA, 4-amino pyridine (4-AP), apamin, caesium or barium affected the oxytocin current. This current is thus at least in part carried by sodium. 5. The activation of the oxytocin current as a function of the membrane potential could be quantitatively simulated using a Boltzmann equation, suggesting that oxytocin acts by inducing the opening of a voltage-dependent channel which can exist in either of two states, open or closed. 6. Lowering the extracellular calcium concentration from 2 to 0.1 mM, while keeping the magnesium concentration constant at 1 mM, enhanced the response to oxytocin. This low calcium-induced potentiation of the oxytocin current was 1.4-3-fold and was reversible. 7. We conclude that oxytocin increases the excitability of vagal neurones by generating a persistent, voltage-gated current which is sodium dependent, is insensitive to TTX and is modulated by divalent cations.
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PMID:Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current. 129 30

The general pharmacological profile of 7-fluoro-1-methyl-3-(methylsulfonyl)- 4(1H)-quinolone BTS 53 554, CAS 76568-68-8), the main metabolite of a new vasodilator, flosequinan (BTS 49 465), was investigated. 1. The central nervous system: BTS 53 554 at the dose of 30 mg/kg i.v. caused an increase in respiratory rate and a sedation in general behavior in rats. The drug also inhibited acetic acid-induced writhing and slightly decreased normal body temperature in mice. However, the drug at the doses up to 30 mg/kg i.v. had little effect on the spontaneous movement, hexobarbital-induced hypnosis, reserpine-induced hypothermia and motor coordination in mice. The drug showed neither anticonvulsant nor analgesic actions in mice. Furthermore, it had no effect on the spontaneous EEG, sleep-wakefulness cycle and EEG arousal response in rabbits at doses up to 10 mg/kg intravenously. 2. The somatic nervous system: BTS 53 554 induced no muscle relaxation in mice and exerted no local anesthetic action in guinea pigs by corneal reflex method. In addition, it had little effect on the neuromuscular transmission in cats. 3. The autonomic nervous system and smooth muscle: BTS 53 554 showed no effect on the sympathetic ganglionic transmission in cats. In isolated smooth muscles, at doses up to 10(-3) mol/l it showed little effect on the acetylcholine- or barium chloride-induced contraction of guinea-pig ileum, norepinephrine-induced contraction of rat vas deferens or oxytocin-induced contraction of nonpregnant rat uterus. However, it inhibited non-competitively norepinephrine-induced contraction of isolated rat aorta at 10(-4) mol/l or more and serotonin-induced contraction of isolated rat fundus at 3 x 10(-4) mol/l or more. In the isolated guinea-pig ileum, the drug slightly inhibited the histamine-induced maximal contraction at 10(-3) mol/l. These results suggest BTS 53 554 had no specific effect on norepinephrine, serotonin, acetylcholine or histamine. The drug relaxed isolated guinea-pig trachea at 3 x 10(-5) mol/l or more and inhibited the spontaneous movement of isolated pregnant rat uterus at 10(-4) mol/l or more, although these actions were extremely weaker than those of isoproterenol (isoprenaline). BTS 53 554 also showed a slight inhibition of uterus movement in anesthetized rats at 30 mg/kg intravenously. 4. The digestive system: BTS 53 554 tended to inhibit the gastrointestinal propulsion in mice and showed a slight inhibition of gastric and intestinal motilities in rats at 10 mg/kg intravenously.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological properties of the main metabolite of flosequinan. 133 57

Pharmacological effects of a new vasodilator, flosequinan (7-fluoro-1-methyl-3-(methylsulfinyl)-4(1H)-quinolone, BTS 49 465, CAS 76568-02-0) on the central nervous system, somatic nervous system, autonomic nervous system and smooth muscle, digestive system and miscellaneous organs were investigated. 1. The central nervous system: Flosequinan inhibited acetic acid-induced writhing at doses of more than 30 mg/kg p.o. and decreased body temperature and tended to decrease spontaneous movement slightly in mice at a dose of 100 mg/kg p.o. However, flosequinan had little effect on hexobarbital-induced hypnosis, reserpine-induced hypothermia and motor coordination and lacked anticonvulsant and analgesic activities in mice. Flosequinan had little effect on general behavior in rats and did not have any effect on spontaneous EEG and EEG arousal response in rabbits. 2. The somatic nervous system: Flosequinan did not cause muscle relaxation in mice and had little effect on neuromuscular transmission in cats. No local anesthetic activity was exhibited through inhibition of the corneal reflex in guinea pigs. 3. The autonomic nervous system and smooth muscle: Flosequinan produced a relaxation of the isolated trachea of guinea pigs at concentrations of more than 3 x 10(-5) mol/l, but its potency was very weak in comparison with that of isoproterenol (isoprenaline). Flosequinan inhibited spontaneous motility of the isolated uterus of pregnant rats at concentrations higher than 10(-4) mol/l and the motility of the uterus of non-pregnant rats in vivo was inhibited at 30 mg/kg i.v. Flosequinan does not seem to exert any on norepinephrine, serotonin, acetylcholine or histamine. This is supported by the fact that at concentrations of 10(-4)-3 x 10(-3) mol/l non-competitive inhibition was observed with regard of the contractions of the isolated aorta and vas deferens of rats induced by norepinephrine, the contraction of isolated rat stomach induced by serotonin, the contraction of isolated guinea-pig ileum induced by acetylcholine, histamine and barium chloride and the contraction of the isolated uterus of non-pregnant rats induced by oxytocin. However, flosequinan was more potent as a relaxant of vascular than of these other smooth muscles. The drug was slightly inhibitive at a high dose of 30 mg/kg i.v. with regard of the contraction of nictitating membrane induced by stimulation of preganglionic sympathetic nerve in cats. 4. The digestive system: Flosequinan at 100 mg/kg p.o. inhibited intestinal propulsion in mice and inhibited spontaneous motility of stomach and duodenum of rats at a dose of 30 mg/kg i.v.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:General pharmacological properties of the new vasodilator flosequinan. 147 41

1. The crude aqueous/alcoholic extract (CE) of Mandevilla illustris (Apocynaceae) rhizomes was analysed against contractile response elicited by bradykinin (BK), lysyl-bradykinin (L-BK), oxytocin(Ot), acetylcholine (Ach), angiotensin II (AII) and barium chloride (BaCl2) in the isolated uterus of the rat. 2. The CE of this plant (0.5-2.0 mg/ml) caused a parallel and concentration-related rightward displacement of BK and L-BK contractile responses. Schild plot revealed a linear relationship (r close to one) and yielded nominal PA2 values of 3.6 and 3.2 respectively, but the slopes were significantly different from unity. 3. However, the anti-BK action of the CE of M. illustris was not selective to kinin action, since in the same range concentration the CE also affected uterine contractile responses induced by Ot, Ach, AII and BaCl2.
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PMID:Antagonism of kinin-induced contraction of isolated rat uterus by the crude hydroalcoholic extract from Mandevilla illustris. 205 Feb 94

Sensitivity to phenylephrine, isoproterenol, serotonin, oxytocin, acetylcholine and barium chloride of vas deferens uterus und fundus strip was studied comparatively in hepatectomized and sarcoma-45, sarcoma-M1, Walker carcinosarcoma and Zajdela ascites hepatoma bearing rats. The contractile response to monoamines and oxytocin was considerably lower or absent at certain periods after hepatectomy or tumour grafting. Effects of biogenic amine antagonists were also substantially altered. The response to isoproterenol, acetylcholine and barium chloride remained unchanged. Apparently a selective alteration of a response of visceral smooth muscles mediated through alpha-adrenergic and D-serotonin receptors occurred not only during the tumour growth but also in the case of active (extensive) proliferation of the normal tissue.
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PMID:[The monoaminergic receptors of the internal organs in rats with a tumor and after partial hepatectomy]. 217 98

The facilitation of peptide secretion from the neurohypophysis induced by increasing stimulation frequency is accompanied by action potential (AP) prolongation. One hypothesis argues that inactivation of potassium channels in the neural lobe terminal membranes, under these conditions, is the underlying mechanism which leads to AP prolongation, and, therefore, increased calcium entry and secretion per AP. Therefore, factors which are known to cause AP prolongation, such as stimulus frequency and potassium channel blocking agents, were studied and compared with regard to their ability to augment electrically evoked release of oxytocin (OT) and vasopressin (VP) from isolated rat neurointermediate lobes (NILs). OT release (to a constant applied stimulus of 600 spikes) was maximally facilitated by increasing frequency up to a rate of 30 Hz, whereas VP release in the same stimulus paradigm was maximal between 12 and 20 Hz. Tetraethylammonium (TEA), 4-aminopyridine (4AP) and barium each caused a significant augmentation of AP-dependent, electrically stimulated hormone release, without affecting basal levels. The magnitude of the effect of the K channel blocking agents was inversely related to the frequency of the applied stimulus. Application of either 4AP or TEA caused a shift in the range of frequency dependence for OT such that maximal release was seen at a stimulus frequency of 12 Hz, but there was no comparable change in the pattern of VP release. The maximal effects of TEA and 4AP were additive indicating that the NIL terminals have two types of K channels which appear to be involved in the regulation of secretion. Addition of the three agents together produced maximal release at a stimulus frequency of 4 Hz, which was not facilitated further by the increase of stimulus frequency to 20 Hz. These data demonstrate the importance of potassium channels in the regulation of VP and OT secretion, and provide indirect support for the spike prolongation hypothesis of frequency facilitated secretion in the neural lobe.
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PMID:Effects of stimulus frequency and potassium channel blockade on the secretion of vasopressin and oxytocin from the neurohypophysis. 244 64

The pharmacological effects of the new antithrombotic drug, cilostazol (6-(4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-qui nolinone, OPC-13013) on the peripheral nervous system and miscellaneous organs were studied. Cilostazol produced a very slight increase in beating rate of the isolated atrium and a very slight increase in contraction of the papillary muscle of guinea pigs induced by cilostazol compared with that of isoproterenol (isoprenaline). The beating rate increasing effect was not antagonized by propranolol and it augmented isoproterenol's effect. When administered intravenously in anesthetized dogs, cilostazol increased blood flow in the coronary, internal carotid, vertebral and femoral arteries and transiently decreased blood flow in the renal and superior mesenteric arteries probably because of blood pressure fall. In anesthetized dogs, cilostazol decreased blood pressure by reducing the resistance in the peripheral blood vessels. An increase in heart rate, cardiac contractile force, myocardial oxygen consumption and respiration rate were also observed. In conscious rats, the drug increased heart rate. Cilostazol produced a slight relaxation of the smooth muscle of all organs except for blood vessels and slightly inhibited spontaneous motility of the isolated uterus of pregnant rats, the isolated ileum of rabbits and the ileum of rats in situ. It was considered that cilostazol had no specific effects against norepinephrine, serotonin, acetylcholine or histamine based on the results that the drug was only slightly antagonistic against the contraction of rabbit aorta induced by norepinephrine and serotonin, the contraction of isolated guinea-pig ileum induced by acetylcholine, histamine and barium chloride and the contraction of the isolated uterus of non-pregnant rats induced by oxytocin. The drug had little effect on the contraction of the nictitating membrane induced by stimulation of the preganglionic sympathetic nerve in the cat. These results suggest that cilostazol had little effect on the autonomic nervous system. Cilostazol slightly inhibited edema induced by carrageenin, but showed no diuretic effect and had little effect on neuromuscular transmission or the secretion of gastric juice, bile and pancreatic juice, and therefore it was considered to have no appreciable effect on the peripheral nervous system or organs except for its vasodilating and cardiac effects.
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PMID:General pharmacological properties of cilostazol, a new antithrombotic drug. Part II: Effect on the peripheral organs. 300 Mar 92


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