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)

Attention is focused on the similarities in primary structure of the egg-laying neurohormone of the pulmonate Lymnaea stagnalis and of the opisthobranch Aplysia californica which both consist of 36 amino acid residues. FMRFamide-like peptides have now been isolated and sequenced from six molluscan species. Besides FMRFamide, two closely related peptides were isolated from the central nervous system of L. stagnalis and sequenced. This indicates that a family of FMRFamide-like peptides exist not only in the molluscs, but also within one species. A molluscan growth hormone, isolated from the brain of L. stagnalis, has been characterized. This small peptide hormone stimulates in vitro a receptor-adenylate cyclase system of mantle edge cells and in vivo the Ca2+-incorporation in the shell edge. The biochemical characterization of three vertebrate-like peptides of L. stagnalis, resembling oxytocin, Arg-vasopressin, and insulin, confirms the immunological findings that gastropods contain peptides which are structurally closely related to mammalian peptides.
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PMID:Molecular properties of various snail peptides from brain and gut. 391 18

The investigation was undertaken to evaluate the direct stimulatory effects of neurohypophyseal hormones upon adenylate cyclase activity in a cell-free, particulate fraction derived from the kidney medulla of various mammalian species. The relative affinity of neurohypophyseal hormones for the receptor component of the adenylate cyclase system (as defined by the concentration of hormone required for half-maximal stimulation) had the order [8-arginine]-vasopressin > [8-lysine]-vasopressin >> oxytocin (AVP > LVP >> OT) for rat, mouse, rabbit, and ox; in the pig, the order was LVP > AVP >> OT. The relative affinities of the three hormones in rat and pig cyclase systems were found to correspond with the relative antidiuretic potencies of these hormones in the intact rat and pig. These findings show that the renal receptor for neurohypophyseal hormones in a particular species exhibits the highest affinity for the specific antidiuretic hormone that occurs naturally in that species. Some of the molecular requirements for the stimulation of rabbit adenylate cyclase were defined by studies of several neurohypophyseal analogs possessing structural changes in positions 1, 2, 3, 4, 5, 8, and 9. This investigation introduces the particulate preparation of renal medullary adenylate cyclase as a tool for the analysis of neurohypophyseal hormone-receptor interactions and indicates that this preparation can be adapted to serve as an in vitro bioassay system for antidiuretic hormonal activity.
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PMID:Neurohypophyseal hormone-responsive adenylate cyclase from mammalian kidney. 433 57

Interactions of hormones stimulating and inhibiting uterine contraction were studied in vitro in uteri from oophorectomized rats. The beta-adrenergic effector, isoproterenol, a potent inhibitor of contraction, produced a dose-related increase of adenylate cyclase and accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) that was inhibitable by propranolol. Oxytocin, which stimulates contraction, effectively inhibited accumulation of uterine cAMP induced by isoproterenol in the presence or absence of theophylline. Prostaglandins E(2) and F(2alpha), each at a maximum effective concentration of 0.5 muM, also inhibited accumulation of cAMP induced by isoproterenol, consistent with their effect in stimulation of uterine contraction. Prostaglandin E(2), but not prostaglandin F(2alpha), stimulated cAMP accumulation in a dose-related manner at concentrations in excess of 0.5 muM. Neither propranolol nor oxytocin inhibited that response. Bovine endometrial adenylate cyclase failed to respond to isoproterenol but was stimulated by prostaglandins E(1) and E(2). When myometrial preparations were studied, isoproterenol stimulation and prostaglandin effects were observed as for whole castrate uterus. The competitive physiological actions of beta-adrenergic effectors on the one hand, and oxytocin and prostaglandins on the other hand, are based on their influences on a myometrial adenylate cyclase. Stimulation of uterine cAMP accumulation by prostaglandin E(2) is due to action at a different and unrelated site.
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PMID:Hormonal interactions in the uterus: inhibition of isoproterenol-induced accumulation of adenosine 3':5'-cyclic monophosphate by oxytocin and prostaglandins. 434 7

Clinical research has shown that prostaglandins (PGs) play an important role in every phase of human reproduction. The logical consequence of early basic biological research into PGs is the current interest in clinical evaluation of PGs as agents to induce labor and abortion and to stimulate menstruation. This is a review of the current literature dealing with PG research. Both PGF2alpha and PGE2 are known to induce labor at term when administered by intravenous infusion. Their relative effectiveness as compared to oxytocin has yet to be assessed. Intravenous infusion of PGE1, PGE2, and PGF2alpha will also induce abortion. Current research is being directed toward finding more practical methods of administration than continuous intravenous infusion. There is hope that PGs will be able to be used as a once a month contraceptive administered at the time of expected menstruation following exposure and a possible unwanted pregnancy. The exact mechanism of action of PGs on smooth muscle is still largely unknown. The differences in response of a specific muscle to different PGs have also not received much research attention. Little is known, for example, regarding the action of PGs on the cervix as opposed to the rest of the uterus. Particularly unknown is the mechanism of action of PGs at the molecular level. In most of the situations studied, PGs seem to stimulate adenyl cyclase activity and cyclic adenosine monophosphate formation or accumulation.
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PMID:Developing applications of prostaglandins in obstetrics and gynecology. 462 50

The interrelationship of several physiological receptors which influence the hydroosmotic response of the toad urinary bladder was studied employing neurohypophyseal peptides, prostaglandin E(1), theophylline, and cyclic nucleotides. The binding property of agonists (pD(2)), synergists (pS(2)), competitive antagonists (pA(2)), and noncompetitive antagonists (pD(2)') was determined after a suitable methodology had been developed. A series of neurohypophyseal peptides was examined in detail for their catalytic activity. It was found that the replacement of the hydroxy radical of the tyrosine residue in oxytocin by a methoxy and then by an ethoxy radical led to a progressive decline in the catalytic activity of the hormone-corresponding to a change from agonist to partial agonist to competitive antagonist. [4-Leucine]-mesotocin behaved as a competitive antagonist of oxytocin. Prostaglandin E(1) (PGE(1)) was found to be a noncompetitive inhibitor of neurohypophyseal peptides and theophylline; whereas the maximal hydroosmotic response of the bladder to [2-O-methyltyrosine]-oxytocin and theophylline was greatly depressed by PGE(1), the response to saturating concentrations of oxytocin was only slightly diminished-a finding which reveals a "receptor reserve" for oxytocin. Saturating concentrations of [2-O-ethyltyrosine]-oxytocin, inactive per se, potentiate theophylline-disclosing a "threshold phenomenon" for the mediation of neurohypophyseal hormone action. It is concluded that neurohypophyseal peptides are capable of producing graded effects on adenyl cyclase both below and above the range of enzyme activity which evokes graded changes in membrane permeability.
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PMID:Threshold and receptor reserve in the action of neurohypophyseal peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder. 543 69

Extracellular application of some peptides (oxytocin, Lys-vasopressin, Leu-enkephalin) to neuron RPal induced pacemaker potentials generation and initiated or increased bursting activity. Norepinephrine and prostaglandins E1 and E2 effects on neuron RPal electric activity were qualitatively similar to those produced by oxytocin and Lys-vasopressin. Dibutyryl-cAMP, papaverine (phosphodiesterase inhibitor) and sodium fluoride (nonspecific adenylate cyclase activator) induced or potentiated bursting activity. It is supposed that oxytocin, Lys-vasopressin, Leu-enkephalin, norepinephrine and E group prostaglandins effects are mediated by intracellular processes related to activation of adenylate cyclase and increase of cAMP level in the neuron.
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PMID:[Reactions of an identified edible snail neuron to application of peptides, mediators, prostaglandins, and cyclic nucleotides]. 611 55

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

The effects of oxytocin and methacholine on cyclic nucleotide levels in estrogen-primed rabbit myometrium were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiesterase inhibitor. In the absence of MIX, methacholine increased guanosine 3',5'-cyclic monophosphate (cGMP) levels at a time when contraction was decreasing, but had no influence on adenosine 3',5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin did not elevate cGMP, but rapidly decreased cAMP levels. MIX (1 mM) increased both cAMP and cGMP levels. Oxytocin or methacholine further increased cGMP, indicating activation of guanylate cyclase. Oxytocin- but not methacholine-induced stimulation of guanylate cyclase was abolished in Ca2+-free solution. Oxytocin increased cAMP over the levels produced by MIX alone, whereas methacholine decreased cAMP below the MIX control values; these effects were insensitive to indomethacin. Tissue levels of cGMP and cAMP did not directly correlate with isometric tension. The results also indicate that both oxytocin and methacholine stimulate guanylate cyclase but have opposing effects on adenylate cyclase of rabbit myometrium.
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PMID:Effects of oxytocin and methacholine on cyclic nucleotide levels of rabbit myometrium. 615 88

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 effects of arginine-vasotocin and nucleotides on the steady-state kinetics of the adenylate cyclase activity in the epithelial cell membranes of the bullfrog (Rana catesbiana) bladder were studied. Arginine-vasotocin stimulated adenylate cyclase more effectively than oxytocin or arginine-vasopressin, with respect to both the maximal hormonal activation ratio relative to basal, and the hormone concentration yielding a half-maximal response (apparent Km). Arginine-vasotocin, GTP and its analogue guanyl-5'-yl imidodiphosphate (Gpp(NH)p) increased the Vmax of the basal adenylate cyclase activity, but showed no effect of the apparent Km of the system for ATP. In addition, Gpp(NH)p enhanced the arginine-vasotocin-stimulated adenylate cyclase activity, further increasing the Vmax, while GTP showed no statistically significant effect. Dual effects of GDP were apparent: it was stimulatory at 1 x 10(-5) mol/l and inhibitory at 1 x 10(-3) mol/l, on both the basal and the arginine-vasotocin-stimulated adenylate cyclase activity. Guanosine 5'-monophosphate, CTP, UTP and ITP showed no apparent effect on the enzyme activity. Sodium fluoride acted in the same manner as GTP on the adenylate cyclase system, increasing only basal activity. Adenylate cyclase activities exhibited pH optima that were less distinct in the presence than in the absence of Gpp(NH)p. The Arrhenius plot of the temperature experiment showed that a high-energy step was involved for activation by Gpp(NH)p or arginine-vasotocin. When the relative activation ratios by arginine-vasotocin at different ATP concentrations were studied, a distinct activation optimum was shown at 2.5 x 10(-4) mol ATP/l, either in the absence or presence of Gpp(NH)p. The possibility that GTP, GDP nd ATP play a regulatory role in the epithelial cells of the bullfrog bladder by adjusting the responsiveness of the system to a natural hormone, arginine-vasotocin, is discussed.
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PMID:Stimulatory and inhibitory effects of guanine nucleotides on arginine-vasotocin-sensitive adenylate cyclase in the epithelial cell membranes of the bullfrog bladder. 660 97


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