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)

The inactivation of the neurohypophyseal hormones arginine vasopressin and oxytocin, both 14C-labelled in the C-terminal glycine residue, by enzymes present in kidney homogenates of various species has been investigated, and some of the enzymes responsible have been partially purified and characterized. The Leu-Gly peptide bond of oxytocin is generally most effectively cleaved by kidney homogenates, although with certain species enzymic activity hydrolyzing the Pro-Leu bond is significant. Degradation of arginine vasopressin is slower than oxytocin in all species studied, and appears to occur by a different overall mechanism since cleavage of the Pro-Arg bond is more significant than hydrolysis of the Arg-Gly bond. The enzyme releasing glycinamide from oxytocin and the "Post-Proline Cleaving Enzyme", which releases C-terminal dipeptide from oxytocin and arginine vasopressin, were partially purified from lamb kidney by ammonium sulfate fractionation and column chromatography. The two enzymes are shown to be separate entities with different pH profiles. The prolyl peptidase activity released the C-terminal dipeptides from oxytocin and arginine vasopressin at similar rates and was inhibited by p-chloromercuriphenylsulfonic acid, 1,10-phenanthroline, L-1-tosylamido-2-phenylethylchloromethyl ketone, Co2+, Ca2+, and Zn2+, but significantly enhanced by dithiothreitol. The prolyl peptidase preparation cleaves proline-containing peptide substrates at the Pro-X bond. The rate of cleavage is dependent on the nature of residue X and with the conditions used there is no cleavage when X equals Pro; however, cleavage occurs when X is a D isomer: [Mpr1, D-Arg8] vasopressin is inactivated at a rate similar to [Mpr1, Arg8]- and [Mpr1, Lys8] vasopressin, suggesting that the known prolonged biological action of [Mpr1, D-Arg8] vasopressin is not due to resistance to the prolyl peptidase. In all characteristics tested the lamb kidney prolyl peptidase was identical to the post-proline cleaving enzyme isolated earlier from human uterus. In vivo experiments in the cat suggested that both the glycinamide-releasing enzyme and post-proline cleaving enzyme are present and effective in inactivating neurohypophyseal hormones in the intact animal.
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PMID:Partial purification and characterization of post-proline cleaving enzyme: enzymatic inactivation of neurohypophyseal hormones by kidney preparations of various species. 0

Slices from ox neurohypophyses were incubated in a calcium-free medium with the ionophores A23187 or X537A. X537A (5 X 10(-5) mol/l) caused a marked release of vasopressin, neurophysin and protein to the medium. A23187 (2 X 10(-5) mol/l) did not cause any release by itself, but when Ca2+ was added to the medium in the presence of the ionophore, an increase in the release of vasopressin, neuorphysin and protein occurred. Release of lactate dehydrogenase and peptidase were not affected by the ionophores. The secretion caused by A23187 was abolished by D600 (a verapamil analogue) (2 X 10(-5) mol/l) whereas the effect of X537A was unchanged. The effects of X537A were strongly inhibited by removal of sodium from the medium. Re-addition of sodium to the medium caused a marked release. Gramicidin (10(-6) or 5 X 10(-5) mol/l) had no effect on secretion. Efflux of 45Ca2+ from pre-loaded slices was drastically reduced in a sodium-free medium. X537A caused an increase in the efflux rate of 45Ca2+ both in medium with a normal concentration of sodium and when slices had been incubated in a sodium-free medium. A23187 and X537A both released 45Ca2+ from a neurohypophyseal mitochondrial fraction. When sodium in a concentration of 20 mmol/l was added to this fraction, the Ca2+ accumulation was inhibited. This effect was reduced by inorganic phosphate up to a concentration of 2 mmol/l.
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PMID:Calcium and stimulus secretion coupling in the neurohypophysis. V. The effects of the Ca2+ ionophores A23187 and X537 A on vasopressin release and 45Ca2+ efflux; interactions with sodium and a verapamil analogue (D600). 6 Aug 66

Amphibian epithelia have been used as models for studying the effects of psychotropic drugs on membrane transport. Several of these agents added to the internal or to the external media, at concentrations greater than 10(-3) M, had inhibitory, "ouabain-like" effects on Na transport. In contrast, stimulatory, "vasopressin-like" effects were seen at lower concentrations. The stimulation was additive to that of oxytocin if the drug was present in the external solution but nonadditive if in the internal solution. On water transport, harmala alkaloids had a vasopressinomimetic action in toad skin, while inhibition was seen with Li and amitriptyline. To account for these multiple effects, it is hypothesized that psychotropic drugs act on the following cell targets: the Na pump, the cyclic nucleotide system, microtubules, and membrane calcium sites at the outer barrier of the epithelium. Direct, biochemical evidence is needed to substantiate this hypothesis.
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PMID:Vasopressin-like effects of psychotropic drugs in amphibian epithelia. 10 41

Recent data on the effects of neurohypophysial peptides at the cellular level are discussed with respect to the two basic processes involved in peptide hormone action--i.e., specific recognition of the information contained in the hormonal molecule and the transformation of this information into a stimulus leading to the final biological response. Four main aspects of this general problem are considered. A. Hormone-Receptor Interaction: Recent contributions in this field concern partial analysis of the three-dimensional conformation of oxytocin and vasopressin moleculal cells of the mammalian kidney. Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration. Models have been proposed that provide a valuable clue to the interpretation of structure-activity relationships among natural hormones and many structural analogues. Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney. B. Stimulus Generation: The nature of the primary stimulus generated by hormone-receptor interaction is still unknown. In the epithelial target cells of the amphibian skin and bladder and of the mammalian kidney, one of the first consequences of hormone-receptor interaction is the activation of membrane-bound adenylate cyclase. Analysis of the correlations between hormonal binding and adenylate cyclase activation suggests that activation is a function of receptor occupation rather than of the number of hormonal molecules interacting with the receptor per unit of time. On medullary adenylate cyclase of pig kidney, the relation between receptor occupancy and enzyme activation was found to be complex and nonlinear. The effects of several agents (calcium, nucleotides) on receptor occupancy and adenylate cyclase activation have been described. In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides.
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PMID:Stimulus-response coupling in neurohypophysial peptide target cells. 17 91

The question as to whether calcium can be considered to be a mediator of oxytocin-induced myometrial contraction has been investigated. Assuming that the contraction is linearly proportional to the myoplasmic calcium concentration, several possible molecular mechanisms leading to its increase (calcium release from the cell membrane, acceleration of calcium transport from extracellular space by a 'gate' mechanism, release from intracellular organelles, blockade of calcium pumps) were modelled on an analog computer. The oxytocin intervention in the calcium distribution was mimicked by a discontinuous change of the appropriate rate constants. The computed transient simulating the myoplasmic calcium concentration was then compared with an experimental time profile of uterine tension. The result of screening the models shows that oxytocin must act predominantly via release of calcium bound to the cell membrane. A quantitative comparison, however, requires that the kinetics of oxytocin distribution in myometrium also be considered in the model. The problem treated in this paper demonstrates the possibilities and limitations of a screening procedure based upon direct comparison of time profiles of experimental processes with several computed model alternatives.
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PMID:The use of dynamic models to study the role of calcium in the oxytocin-induced contractions of the uterus. 19 65

Activation of 2-deoxyglucose transport in isolated rat fat cells by insulin is dependent upon the presence of Ca2+ in the external medium. When calcium concentration is kept below 100 micron, insulin acts like a partial agonist, giving only half of the maximal activation obtained normally with a millimolar concentration of this ion. Oxytocin, whose insulin-like action on adipocytes activates glucose oxidation by these cells, was found to be unable to affect the rate of 2-deoxyglucose transport. This, together with previous observations, suggests that calcium ions play a role in the mechanism of insulin action possibly by binding selectively to membrane sites involved in the transmission of the hormonal message to the glucose carrier. Oxytocin seems to trigger only intracellular glucose metabolism and it appears that there is an absolute requirement for calcium ions in the activation of a still unknown membrane signal.
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PMID:Calcium as modulator of the hormonal-receptors-biological-response coupling system. Effects of Ca2+ ions on the insulin activated 2-deoxyglucose transport in rat fat cells. 20 16

Rat and bovine adrenal cortical microsomal fractions isolated at 27,000 x g and 105,000 x g accumulated Ca2+ by a nonmitochondrial, ATP-dependent uptake system that was stimulated by ammonium oxalate. ACTH (2 mU/ml) significantly increased Ca2+ uptake in bovine adrenal cortical microsomes and in adrenal microsomes from acutely hypophysectomized rats, but only when the hormone was preincubated with intact tissue and not when it was added after homogenization. ACTH did not stimulate C2+ uptake in adrenal microsomes isolated from nonhypophysectomized, ether-stressed rats, in which basal Ca2+ uptake was higher than that observed in microsomes from hypophysectomized animals. The peptides oxytocin, insulin, and TSH did not stimulate Ca2+ uptake by adrenal cortical microsomes. ACTH preincubated with intact tissue had no effect on Ca2+ uptake in microsomes from liver, kidney, esophagus, or aorta. cAMP, 5'-AMP, and several other nucleotides, nucleosides, and related compounds stimulated adrenal cortical microsomal Ca2+ uptake by as much as 540% of control. The stimulatory effects of nucleotides, unlike those of ACTH, were apparent even when the agents were added after homogenization. However, like ACTH, the nucleotides were unable to stimulate Ca2+ uptake when they were added to isolated membrane vesicles during Ca2+ uptake measurements. It is suggested that the microsomal Ca2+ uptake system may respond to physiological stimulants and regulate Ca2+ availability in the intact cell.
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PMID:The effect of adrenocorticotropin and nucleotides on Ca2+ uptake in adrenal cortical microsomal vesicles. 21 5

The oxytocin-sensitive myoepithelial cells of the mammary gland form a system with characteristics of a potentially useful model for studying the mechanism of action of oxytocin and coupling phenomena of excitation-contraction. Our objectives were to develop a method for isolating mammary actomyosin, to determine the amount of actomyosin in the glands of lactating and nonlactating animals, and to investigate control of contractile protein interaction. Actomyosin in mammary glands represented a substantial portion of the soluble protein in the gland ranging from 9% of the total in lactating to 17% in weaned rats. The isolated actomyosin had a molecular composition like that of actomyosin of smooth muscle and the isolated actomyosin contained a light chain kinase that phosphorylated the 20,000 dalton light chain of myosin (L20). The kinase isolated as a component of actomyosin preparations did not show calcium control, but it did when isolated from mammary cytosol. Strips of involuted mammary tissue from rats developed tension when oxytocin was added to the bathing medium; thus, the myoepithelial cells appeared to retain their sensitivity to oxytocin even in nonlactating animals and may be a useful model for studying the action of oxytocin. We suggest that one of the final steps in the milk-ejection reflex is phosphorylation of myosin causing a contraction of the myoepithelial cells of the mammary gland.
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PMID:Actomyosin from mammary myoepithelial cells and phosphorylation by myosin light chain kinase. 21 47

The responses of isolated frog skin to 5-hydroxytryptamine (increased active sodium transport and decreased passive chloride permeability) are diminished by incubation with the enzymes neuraminidase and N-acetylneuraminic acid aldolase but only in the absence of Ca2+ and presence of EDTA. The responses induced by oxytocin, adrenalin and aldosterone are unaffected by enzyme treatment.
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PMID:Selective destruction of 5-hydroxytryptamine receptors by neuraminidase. 31 8

A microsomal fraction resembling striated muscle sarcoplasmic reticulum was isolated from uterine smooth muscle. ATP induces calcium accumulation in this fraction. Increased temperature enhances calcium accumulation and calcium-activated ATPase. In the absence of ATP, approximately 35% of the intrinsic calcium exchanges with the 45Ca in the incubation medium. In the presence of ATP, exchange of intrinsic calcium with 45Ca increases by an amount which equals the ATP-dependent calcium binding. In preparations partially preloaded with calcium, a steady state of bound calcium is reached when the ATP is exhausted. Calcium is released under these conditions by prostaglandins E2 and F2alpha, but not by PGF1beta. The antibiotic ionophores X537A and A23187, as well as oxytocin, also release calcium previously accumulated under ATP stimulation. None of these agents, with the exception of oxytocin, release intrinsic calcium. Thus, the effect of prostaglandins resembles that of the ionophores, suggesting an ionophoretic action of these prostaglandins. The release of calcium conforms with the in vivo smooth muscle contracting action of these agents.
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PMID:Effects of prostaglandins and oxytocin on calcium release from a uterine microsomal fraction. 32 Feb 10


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