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)

An accumulation of 3H-labelled inositol phosphates is observed when prelabelled rat superior cervical sympathetic ganglia are exposed to [8-arginine]vasopressin or to muscarinic cholinergic stimuli. The response to vasopressin is much greater than the response to cholinergic stimuli. The response to vasopressin is blocked by a V1-vasopressin antagonist, and oxytocin is a much less potent agonist than vasopressin. Vasopressin causes no increase in the cyclic AMP content of ganglia. These ganglia therefore appear to have functional V1-vasopressin receptors that are capable of activating inositol lipid breakdown, but no V2-receptors coupled to adenylate cyclase. The first [3H]inositol-labelled products to accumulate in stimulated ganglia are inositol trisphosphate and inositol bisphosphate, suggesting that the initiating reaction in stimulated inositol lipid metabolism is a phosphodiesterase-catalysed hydrolysis of phosphatidylinositol 4,5-bisphosphate (and possibly also phosphatidylinositol 4-phosphate). This response to exogenous vasopressin occurs in ganglia incubated in media of reduced Ca2+ concentration. The physiological functions of the V1-vasopressin receptors of these ganglia remain unknown.
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PMID:Rapid accumulation of inositol phosphates in isolated rat superior cervical sympathetic ganglia exposed to V1-vasopressin and muscarinic cholinergic stimuli. 614 75

Adenosine 3':5' monophosphate3 (cAMP) and guanosine 3':5' monophosphate (cGMP) are known to participate in the regulation of proliferation and differentiation, the processes intimately associated with maturation of the neonate. We have therefore examined their content in the physiological nutrient of the mammalian neonate, the mother's milk. Widely fluctuating concentrations between 0.1 and 0.7, and between 0.01 and 0.15 nmol/ml, were found for cyclic AMP and cyclic GMP, respectively. Concentrations in human breast milk changed during the 5-to 15-min period of one nursing, during any 24-h period, and also during the total lactation period. Levels of cyclic GMP were generally less fluctuating and were lower during afternoon and evening; they were relatively high at the start of lactation and levelled off during the postpartum period. The ratio of the two cyclic nucleotides also fluctuated widely and was significantly different from the ratio determined on blood plasma collected at the same time. Oxytocin injection had no effect on cyclic AMP content of rat milk. The stomach content of the nucleotide in rat pups remained high for at least 1 h after suckling indicating that cyclic nucleotides remain available for intestinal absorption; whether they have any physiological function in the neonate will have to emerge from further studies.
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PMID:Cyclic nucleotides in breast milk. 625 24

The binding of vasopressin to human circulating blood cells was examined. Direct binding studies with preparations of single cell types indicated that the mononuclear phagocyte system is almost entirely responsible for binding of the hormone. Binding of 125I-8-L-arginine vasopressin (AVP) (40 pM) in the presence of excess unlabeled hormone was saturable (2.8 +/- 0.4 fmol/2 x 10(6) cells per ml), was linear with cell number, was dependent upon the concentration of the radioligand used, and was reversible. Binding equilibrium was achieved in 30--40 min at 22 degrees C. Scatchard analysis of binding at this time showed an apparent dissociation constant of 25 +/- 0.21 pM, providing an estimate of 640 +/- 80 sites/cell. Pretreatment of the cells with cytochalasin B, an agent that can block phagocytosis, did not modify radioligand binding, which indicates that 125I-AVP uptake by the cells is due to binding and not to endocytosis. Specificity of vasopressin-sensitive sites on mononuclear phagocytes was demonstrated with a series of vasopressin analogues with various degrees of antidiuretic potency, and with peptide hormones that bind to specific receptors on circulating blood cells but that lack antidiuretic activity. AVP (40 pM) elevated the intracellular level of cyclic AMP from 137 +/- 8.6 to 350 +/- 20.5 pmol/mg cell protein. The binding affinities of the various analogues were correlated with their ability to stimulate intracellular cyclic AMP synthesis (Lys8-vasopressin less than deamino(8-D-Arg)-vasopressin less than oxytocin).
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PMID:125I-8-L-arginine vasopressin binding to human mononuclear phagocytes. 626 2

When rat myometrium that had been depleted of Ca by incubation with 3 mM EGTA for 50 min was challenged with 10(-2) unit/ml oxytocin, it showed sustained contraction in a medium with no added Ca (Ca-free contraction). It also showed Ca-free contraction of similar magnitude in the presence of 1 mM EGTA. The effects on this contraction of divalent cations (Co2+, Ni2+ and Mn2+) singly and in combination with D-600 (3 X 10(-6) M) were investigated. Co2+ and Ni2+ potentiated Ca-free contraction concentration-dependently, and their effects were greater in the presence of D-600. In contrast, Mn2+ evoked a triphasic response; first transient potentiation, second relaxation, and third persistent increase in tension. D-600 did not block the first or second, but blocked the third, resulting in persistence of the second phase of relaxation. The relaxing action of papaverine on Ca-free contraction was not affected by D-600. Isoproterenol and dibutyryl cyclic AMP also relaxed the contraction.
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PMID:Oxytocin-induced Ca-free contraction of rat uterine smooth muscle: effects of divalent cations and drugs. 626 5

Mucosal acidification (from pH 8.1 to 6.0) reversibly inhibited the hydroosmotic responses to oxytocin, cyclic AMP and 8-bromo-cyclic AMP in frog urinary bladder. These inhibitory effects were only observed in the presence of a permeant buffer in the apical medium and could also be elicited by CO2 bubbling, even when the mucosal pH was clamped at 8.1. Acid pH reduced the oxytocin-induced net water flux faster than norepinephrine or oxytocin removal and the difference was especially important at low temperature. The time course of recovery from acid pH inhibition was, at 20 degree C, similar to that of the hormonal action, but when the medium temperature was reduced to 6-7 degrees C, the recovery from acid pH inhibition paradoxically became faster while the oxytocin action was markedly slowed down (t 1/2 of changes in net water fluxes (expressed in min): oxytocin addition at 20 degrees C, 6.2 +/- 0.9; at 6 degrees C, 24 +/- 3; oxytocin removal at 20 degrees C, 4.7 +/- 0.8; at 6 degrees C, 22 +/- 3; pH inhibition at 20 degrees C, 2.6 +/- 0.2, at 6 degrees C 2.5 +/- 0.2; recovery from pH 6 at 20 degrees C 6.5 +/- 0.9; at 6 degrees C, 2.7 +/- 0.3). These results can be explained by accepting two main loci sensitive to medium acidification: (1) the cyclase system and (2) an intracellular, temperature-independent, post-cyclic AMP site. The fact that the intramembranous particle aggregates associated with the oxytocin-induced water permeability increase did not disappear after the flow inhibition by acid pH at low temperature suggests that the second effect could be located at the water channel itself.
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PMID:Cellular pH and water permeability control in frog urinary bladder. A possible action on the water pathway. 627 53

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

The effect of 8-L-arginine vasopressin (AVP) on biosynthesis of prostaglandins in human mononuclear phagocytes was examined. AVP, oxytocin, and deamino-(8-D-arginine) vasopressin (dDAVP) affected prostaglandin biosynthesis in a rank order that parallels their pressor but not antidiuretic activity (AVP greater than oxytocin greater than dDAVP). Radioimmunoassay, incorporation studies using [14C]arachidonic acid and radiometric thin-layer chromatography, revealed prostaglandin E2 (PGE2) to be the only prostaglandin synthesized by the mononuclear phagocytes. While high concentrations of PGE2 elevated cytoplasmic levels of cyclic AMP by five- to sevenfold above basal values, low concentrations of PGE2 that are released by the cells in the presence of AVP failed to increase cyclic AMP content in the cells. However, PGE2 at concentrations that do not alter cyclic AMP levels markedly interferes with the activity of AVP. This effect is, however, very time dependent. Addition of PGE2 to the cells 30 min before AVP, was followed by a period of unresponsiveness to the hormone that lasts at least 30 min. Pretreatment of the cells with indomethacin enhanced the AVP-mediated accumulation of intracellular cyclic AMP level. PGE2 did not modify [3H]AVP binding, indicating that its inhibitory effect on the activity of the peptide is not due to downregulation of vasopressin receptors.
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PMID:Interactions between 8-L-arginine vasopressin and prostaglandin E2 in human mononuclear phagocytes. 630 Jan 91

The onset and offset of the hydrosmotic responses elicited by different agonists in frog urinary bladder, frog skin and isolated frog skin epithelium were studied and compared. The removal of the frog skin supporting layers accelerated the onset of the reactions to oxytocin and 8-bromo-cyclic AMP (8-Br-cAMP), which, however, remained slower than the onset in the urinary bladder. The offset of these actions was not affected by corion removal and was also slower than in the bladder. A marked asymmetry between onset and offset of the hydrosmotic response was observed when the isolated skin epithelium was stimulated with 8-Br-cAMP. The results show that the increases in water permeability elicited by oxytocin and cyclic-AMP derivatives in frog skin and frog urinary bladder, although attributable to the same general mechanisms, present different specific characteristics.
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PMID:The onset and offset of the hydrosmotic response in frog epithelia. 633 67

The hydrosmotic response elicited by oxytocin in the frog skin epithelium (Rana esculenta) was reversibly inhibited by 70% when the medium pH was reduced to 6.2 by CO2 bubbling on the serosal side. On the contrary, the response to 8-bromo cyclic AMP (8 Br-CAMP) was not affected by medium acidification, even after corion removal. In other experiments intracellular pH was measured, employing the dimetyl-oxazolidine-dione distribution technique, in frog urinary bladder and the isolated frog skin epithelium. As previously observed in the case of oxytocin, 8 Br-CAMP increased intracellular pH in frog urinary bladder. Incubation with oxytocin also augmented the intracellular pH in the isolated frog skin epithelium but 8 Br-CAMP did not modify cell proton concentration in this tissue. From previous and present results it can be summarized that: 1) The intracellular alkalinization effect elicited by oxytocin addition and the inhibition in the hydrosmotic response induced by medium acidification were qualitatively similar in both tested target epithelia. 2) On the contrary, a post cyclic AMP step sensitive to changes in intracellular pH was not observed in frog skin, as is the case in frog urinary bladder. 3) The 8 Br-CAMP induced intracellular alkalinization effect was only observed in frog urinary bladder.
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PMID:Cellular pH and the ADH-induced hydrosmotic response in different ADH target epithelia. 644 25

The initiation of a complex cascade of events resulting in the delivery of a healthy newborn appears to involve the integrated actions of the fetus, mother and the placenta. Many putative factors have already been extensively reviewed. Instead of concentrating on the action of estrogen and progesterone, the role of regulators of myometrial activity such as prostaglandins as well as the fetal pituitary-adrenal system, oxytocin, corticosteroids, leukotrienes, platelet activating factor, endotoxin and cytokines to name a few, will be discussed. Nevertheless, there is an increasing weight of evidence suggesting that many of the above agonists converge upon a final pathway of prostaglandin production which subsequently increases myometrial responsiveness. Prostaglandins are involved at levels of myometrial regulation such as myometrial gap junction formation, intracellular calcium flux modulation, synchronisation of myometrial contraction via interaction with oxytocin thus having stimulatory effects on uterine contractility, as well as cervical maturation (via PGE2). Importantly, there has been clinical benefit of a more thorough understanding of the physiology of myometrial regulation at the time of partuition. The approach to the treatment of preterm delivery has improved, eventhough the exact mechanism(s) and cause(s) of this phenomenon remain an enigma. Current tocolytic therapy is not generally prophylactic but commences after labour, contractions and cervical dilatation are underway. Key regulatory pathways have been pin-pointed that present opportunity for tocolysis including:-c-AMP inhibition of contraction by beta-mimetic agents, inhibition of calmodulin-calcium function, inhibition of calcium influx by calcium channel blockers, inhibition of prostaglandin production, modulation of myometrial function by peptide hormones or antagonists (e.g. relaxin, VIP and oxytocin antagonists).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of high risk pregnancies: role of prostaglandins and other mediators. 784 15


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