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)

1. In hepatocytes from starved rats, vasopressin, angiotensin (angiotensin II) and oxytocin stimulated gluconeogenesis from lactate by 25--50%; minimal effective concentrations were about 0.02pM, 1 nM and 0.2 nM respectively. 2. Vasopressin and angiotensin also stimulated gluconeogenesis from alanine, pyruvate, serine and glycerol. EGTA decreased gluconeogenesis from these substrates. 3. Hormonal stimulation of gluconeogenesis from lactate was abolished in the absence of extracellular Ca2+. 4. Insulin did not prevent stimulation of gluconeogenesis by vasopressin or angiotensin. 5. The potency of the stimulatory effects of vasopressin and angiotensin on hepatic gluconeogenesis suggests they are operative in vivo. Also, the data suggest that Ca2+ plays a role in the stimulation by these hormones.
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PMID:Stimulation by vasopressin, angiotensin and oxytocin of gluconeogenesis in hepatocyte suspensions. 74 59

A prostaglandin analog, 16-phenoxy-delta-17,18,19,20-tetranor-prostaglandin-E2-methylsulfonamide, was tested in 5 groups of patients which received 1, 2, or 3 mg of the analog intraamniotically. 29/46 (Groups 1-3) patients receiving only the analog expelled the fetus within 30 hours. In Group 4, 2 mg of the analog was combined with oxytocin. 22/28 expelled the fetus within 30 hours. In Group 5, 15 nulliparous and 1 multiparous woman received 3 mg of the analog together with calcium gluconate, injected intraamniotically. Although the mean induction-abortion time was not significantly influenced, the success rate was higher: 87% aborted within 30 hours and 100% within 36 hours. Clinically, the contractions in this group (5) started earlier and were stronger than in other groups. In all groups, side effects were minimal. Multiparous women responded better to therapy than nulliparous patients. Since the amount of drug influenced both the success rate and the induction-abortion interval considerably and the side effects were few, a new study using 4-mg doses is in progress.
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PMID:Termination of second trimester pregnancy with intraamniotic administration of 16-phenoxy-omega-tetranor-PgE2-methylsulfonamide (SHB 286) alone and combined with oxytocin and calcium gluconate. 75 Jan 89

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

35S-cysteine injected adjacent to the supraoptic nucleus (SON) of the rat is rapidly incorporated into proteins. These 35S-cysteine-labeled proteins in the SON (1-24 h after injection) were separated by polyacrylamide gel electrophoresis, and the distribution of radioactive proteins on the gels was analyzed. 1 h after injection, about 73% of the radioactivity appeared in two peaks (both about 20,000 mol wt). With time, these peaks (putative precursors of neurophysin) decreased, as a 12,000 mol wt peak (containing two distinct neurophysins) increased in radioactivity. Both the 20,000- and 12,000-mol wt proteins are transported into the axonal (median eminence) and nerve terminal (posterior pituitary) regions of the rat hypothalamo-neurohypophysial system. Conversion of the larger precursor protein to the smaller neurophysin appears to occur, in large part, intra-axonally during axonal transport. Six distinct 35S-cysteine-labeled peptides (less than 2500 mol wt), in addition to arginine vasopressin and oxytocin, are also synthesized in the SON and transported to the posterior pituitary where they are released together with labeled neurophysin by potassium depolarization in the presence of extracellular calcium. These data provide support for the hypothesis that the neurohypophysial peptides (vasopressin and oxytocin) and neurophysins are derived from the post-translational clevage of protein precursors synthesized in the SON, and that the conversion process can occur in the neurosecretory granule during axonal transport.
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PMID:Biosynthesis and axonal transport of rat neurohypophysial proteins and peptides. 85 41

1. The time course of changes in specific activities of citrate, lactose and fatty acids in milk during frequent milking, following the I.V. administration of labelled glucose, acetate and chylomicrons in goats has been studied. Peak specific activities of lactose and citrate in milk were reached at 2-3 hr, while peak specific activites of fatty acids were reached at 5-7 hr. 2. Following short I.A. infusions of 24Na, 36Cl, and 42K, peak specific activities in milk were reached in 1 hr or less. 3. The mammary epithelium of lactating goats was found to be virtually impermeable to labelled citrate in both directions. 4. Labelled citrate had an apparent volume of distribution in lactating guinea-pigs mammary slices in vitro similar to that of extracellular space markers. 5. Treatment of goats with large doses of oxytocin markedly increased the permeability of the secretory epithelium to labelled citrate. 6. In the goat mammary gland, citrate, protein and calcium failed to enter milk which had been diluted with isosmotic lactose by intraductal injection, whereas Na, K and Cl did enter, thus tending to restore the concentrations of these ions to normal. 7. It is suggested that citrate, which is formed within the sucretory cell, enters milk not by passage across the apical cell membrane but, in common with lactose and milk protein, by exocytosis of Golgi vesicles. It appears that citrate is held at high concentrations in milk by virtue of the impermeability of the mammary epithelium to the forms in which it occurs in milk.
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PMID:The secretion of citrate into milk. 97 74

The available evidence suggests that hormones and neurophysins are associated exclusively with the neurosecretory granules, each of which contains approximately 6 times 10-4 molecules of each. Hormones and carrier proteins are complexed within the granules and the complexes are densely packed. The processes that keep the intragranular space in osmotic equilibrium with the axoplasm require further study. Freeze-fracture data, as well as studies in which histochemical methods for the detection of glycoproteins were used, suggest that the intragranular aspect of the granule membrane mostly resembles the extracellular half of the plasma membrane; on the other hand, the cytoplasmic aspects of plasma and granule membrane have similar characteristics, which may be important in permitting membrane fusion to take place prior to secretion. Little is known about the molecular species involved in this interaction between granule and plasma membrane, except that calcium is a cofactor in this process. Release is triggered in vivo by propagated action potentials which cause an influx of calcium into the secretory endings. Newly formed granules, and other granules located at the periphery of the endings are preferentially released. Irrespective of the type of stimulation of secretion, release involves the diffusion into the extracellular space of granule core constituents. The best evidence so far in support of this view comes from ultrastructural studies showing images of exocytosis, as well as from biochemical studies demonstrating that hormones and carrier proteins are secreted concomitantly in a great variety of experimental or clinical conditions, without an associated release of granule membrane constituents or of enzymes of cytoplasmic origin. Recovery mechanisms following secretion require new synthesis of granule constituents and restoration of the resting internal concentrations of potassium, sodium, and calcium. Membrane surface area is restored following exocytosis by compensatory endocytosis which involves indiscriminate uptake of extracellular medium into the secretory axon terminals. While much progress has been made in research on the cellular and subcellular processes that take place in neurons which produce, store, and secrete neurohypophyseal hormones and their carrier proteins, neurophysins, many pressing questions remain to be answered. New developments, such as organ culture of supraoptic nuclei94-96 and the recent isolation of a clone of mouse hypothalamic cells capable of synthesizing vasopressin and neurophysin,97 will hopefully allow some of these problems to be solved in the future.
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PMID:A review on neurosecretory granules: their contents and mechanisms of release. 109 Nov 94

Isolated rat neural lobes were incubated in vitro in Locke's solution containing anaesthetic quantities of urethane, pentobarbitone or tribromoethanol. The oxytocin content of the incubation medium was estimated before, during and after stimulation of the tissue by raising the potassium chloride concentration from 5-6 to 56 mmol/l. Urethane (25 mmol/l) significantly potentiated oxytocin release (P less than 0-01) whereas tribromoethanol (0-5 mmol/l) had no obvious effect and pentobarbitone (0-4 mmol/l) significantly (P less than 0-01) inhibited its release. Reduction of the sodium chloride concentration in the medium potentiated the release of oxytocin in each case but did not alter its pattern. Urethane which increased secretion of oxytocin also increased calcium ion uptake by the neural lobes and pentobarbitone which decreased oxytocin release decreased calcium ion uptake. The results may explain why the blood concentration of the neurohypophysial hormones tends to be higher in rats anaesthetized with urethane than with tribromoethanol. Inhibition of hormone release by pentobarbitone suggests that this anaesthetic is unsuitable for use in studies of neurohypophysial hormone release. A partial explanation of the anaesthetic properties of urethane and pentobarbitone may also have been found if the release of neurotransmitter substances is influenced in a similar manner.
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PMID:Potentiation by urethane and inhibition by pentobarbitone of oxytocin release in vitro. 110 67

Halothane and other volatile anesthetics were found to relax uteri maximally contracted by oxytocin and to enhance the relaxant effect of propranolol and other agents (tetracaine, quinidine and chlorpromazine) with local anesthetic properties. Concentration-effect curves for inhibition by propranolol or tetracaine were shifted to the left by halothane. Methoxyflurane, chloroform and diethyl ether also increased the effect of propranolol. The tissue/medium ratio for propranolol was increased by halothane. The uptake of propranolol was saturable and was decreased at 2.5 degrees C, suggesting an active transport mechanism. The increased uptake of propranolol in the presence of halothane was probably insufficient to account for the synergism noted. Inhibition by propranolol and tetracaine was inversely related to the concentration of calcium in the medium. The inhibitory effect of propranolol, tetracaine, quinidine and chlorpromazine appeared to be related to their ability to inhibit calcium transport.
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PMID:Interaction between halothane and propranolol on oxytocin-induced uterine contractions. 111 26

The influence of amantadine on the contractile responses of the rat uterus to oxytocin in the presence of several ionic modifications of the external medium was studied both in situ and in vivo. Oxytocic effects of amantadine were observed in vivo (1 and 5 mg/kg), and in vitro (9.3 times 10-7 M to 2.8 times 10-6 M); possible competitive partial potentiation of the contractile effect of oxytocin was also observed. Amantadine, 9.35 times 10-6, 1.3 times 10-5 and 1.8 times 10-5 M, significantly reduced oxytocic activity. Calcium ions antagonized the oxytocic and antioxytocic effects of amantadine. Excess K+ and the presence of Mg2+ ions (1.8 mM/l and 1.08 mM/l respectively) reversed the antioxytocic effect of amantadine. Propranolol also reversed the antioxytocic effect of amantadine. It is postulated that the oxytocic effect of amantadine may be related to antagonism of calcium; antioxytocic activity may be explained by stabilization of the resting cell membrane, inhibiting ionic flow, and also by its catecholamine-liberating activity.
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PMID:The action of amantadine on the rat uterus: its interaction with oxytocin and the effects of several ionic modifications of the medium. 112 78

The efflux of [3-H]GABA from glial cells in the rat posterior pituitary was followed in isolated glands incubated in the presence of 10-minus 5 M aminooxyacetic acid which is known to inhibit GABA metabolism. Electrical stimulation of the pituitary stalk evoked an increase in the rate of efflux of [3-H]GABA as did elevation of the extracellular potassium concentration. The release of neurophysin from nerve terminals in the gland was also increased by electrical stimulation. The increase in [3-H]GABA efflux appeared to be independent of frequency at 2, 5, or 25 HZ if the number of pulses delivered was kept constant, although stimulation at 10 HZ was more effective than either 2 or 25 HZ. The efflux of [3-H]GABA evoked by 56 mM K+ was inhibited by 50% when calcium was removed from the washing fluid and 3 mM EGTA added, while the response evoked by electrical stimulation was unaffected by this procedure. The electrically induced efflux of [3-H]GABA was inhibited by 50% when choline chloride was substituted for sodium chloride in the washing medium, although it was unaffected by tetrodotoxin (0.8 times 10-minus 6 g/ml). The release of exogenous GABA from the pituicyte glia is compared with that of neurophysin from the nerve terminals in the posterior pituitary, and the results are discussed with reference to possible mechanisms of the glial release process.
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PMID:The release of [3-H]gamma-aminobutyric acid and neurophysin from the isolated rat posterior pituitary. 113 91


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