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)

Total and Na+, K+-ATPase activities have been measured in sections (10 micron thick) from blocks of rat kidney cultured for 5 h at 37 degrees C, pH 7.5, in Glasgow Eagle's Minimum Essential Medium. Synthetic [arginine]vasopressin [( Arg]VP) stimulated ATPase activity in the thick tubular cells of the renal outer medulla over the concentration range 0.01-10 fmol/l, but failed to affect ATPase activity in the proximal and distal convoluted tubules of the cortex. The increase in medullary total ATPase activity induced by [Arg]VP and its analogues was wholly due to stimulation of Na+, K+-ATPase activity. Stimulation of medullary ATPase activity was blocked by [Arg]VP antiserum. The [Arg]VP analogues desmopressin, [lysine]vasopressin, [arginine]vasotocin and oxytocin stimulated medullary Na+, K+-ATPase activity, the three last-named analogues being considerably less potent than [Arg]VP.
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PMID:The stimulation of Na+, K+-ATPase activity in the medulla of the rat kidney by [arginine] vasopressin and its analogues. 632 92

Phasic myometrial contractions utilize mechanisms involving the cycling of calcium into and out of intracellular calcium stores. These studies were performed to determine the effects of 2,5-di(tert-butyl)-1,4-hydroquinone (tBHQ), an endoplasmic reticulum Ca(2+)-ATPase inhibitor, on in vitro isometric myometrial contractions. These studies demonstrated that low concentrations of tBHQ (eg. 10 microM) appear to inhibit intracellular calcium cycling, whereas higher concentrations also inhibit extracellular calcium influx. These combined tBHQ effects markedly suppressed myometrial contractions stimulated in response to various agonists including oxytocin, PGF2 alpha, KCl, ionomycin, and Bay K 8644.
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PMID:Effects of 2,5-di(tert-butyl)-1,4-hydroquinone, an endoplasmic reticulum Ca(2+)-ATPase inhibitor, on agonist-stimulated phasic myometrial contractions. 753 6

The effect of sodium ursodeoxycholate (U) on short-circuit current (SCC), an index of basal and stimulated net ion transport across isolated skins of Bufo arenarum toads, was tested. U inhibited basal SCC when added to the epidermal side of the skins. The inhibitory effect was reversible after rinsing the preparation during 60 min. U also inhibited the natriferic response to oxytocin, db-cAMP and theophylline by 82%, 49% and 47%, respectively. Inhibition of SCC by exposure to U was reversed by the polyene antibiotic nystatin. In turn, SCC induced by nystatin in the amiloride-treated skin was insensitive to U and blocked by ouabain, a Na+, K(+)-ATPase inhibitor. These results strongly suggest that the effect of U is exerted at the apical membrane of sodium transporting cells, and rule out the existence of an additional site of inhibitory action of U.
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PMID:Inhibitory effect of sodium ursodeoxycholate on basal and stimulated short-circuit current across the isolated toad skin. 759 81

This study investigated the underlying mechanisms of oxytocin (OT)-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in acutely dispersed myometrial cells from prepartum sows. A dose-dependent increase in [Ca2+]i was induced by OT (0.1 nM to 1 microM) in the presence and absence of extracellular Ca2+ ([Ca2+]e). [Ca2+]i was elevated by OT in a biphasic pattern, with a spike followed by a sustained plateau in the presence of [Ca2+]e. However, in the absence of [Ca2+]e, the [Ca2+]i response to OT became monophasic with a lower amplitude and no plateau, and this monophasic increase was abolished by pretreatment with ionomycin, a Ca2+ ionophore. Administration of OT (1 microM) for 15 sec increased inositol 1,4,5-trisphosphate (IP3) formation by 61%. Pretreatment with pertussis toxin (PTX, 1 microgram/ml) for 2 hr failed to alter the OT-induced increase in [Ca2+]i and IP3 formation. U-73122 (30 nM to 3 microM), a phospholipase C (PLC) inhibitor, depressed the rise in [Ca2+]i by OT dose dependently. U-73122 (3 microM) also abolished the OT-induced IP3 formation. Thapsigargin (2 microM), an inhibitor of Ca(2+)-ATPase in the endoplasmic reticulum, did not increase [Ca2+]i. However, it did time-dependently inhibit the OT-induced increase in [Ca2+]i. Nimodipine (1 microM), a voltage-dependent Ca2+ channel (VDCC) blocker, inhibited the OT-induced plateau by 26%. La3+ (1 mM), a nonspecific Ca2+ channel blocker, abrogated the OT-induced plateau. In whole-cell patch-clamp studies used to evaluate VDCC activities, OT (0.1 microM) increased Ca2+ current (ICa) by 40% with no apparent changes in the current-voltage relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxytocin induced a biphasic increase in the intracellular Ca2+ concentration of porcine myometrial cells: participation of a pertussis toxin-insensitive G-protein, inositol 1,4,5-trisphosphate-sensitive Ca2+ pool, and Ca2+ channels. 761 2

Oxytocin stimulates phosphoinositide turnover in myometrium. To elucidate whether the coupling mechanism involves the interaction of oxytocin receptor with GTP-binding proteins, we examined oxytocin stimulation of guanosine triphosphatase (GTPase) activity and phospholipase-C activity in rat and human myometrial membranes. Oxytocin consistently stimulated both GTPase and phospholipase-C activities, and both stimulations were attenuated by an antibody directed against the carboxyl-terminals of the GTP-binding proteins, G alpha q and G alpha 11. Neutralization of the antibody by preincubation with antigenic peptide reversed this inhibition. [Thr4,Gly7]oxytocin, a specific oxytocin receptor agonist, stimulated both GTPase and phospholipase-C activities, and the stimulations were also inhibited by anti-G alpha q/11 IgG. Immunoreactive GTP-binding proteins, G alpha q and G alpha 11, and phospholipase-C beta 3 isoforms were present in myometrial membranes. These results indicate that stimulation of phospholipase-C activity by oxytocin in myometrium is mediated via G alpha q, G alpha 11, or a closely related GTP-binding protein, probably coupling to phospholipase-C beta.
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PMID:Oxytocin stimulates myometrial guanosine triphosphatase and phospholipase-C activities via coupling to G alpha q/11. 789 60

Antidiuretic hormone and parathyroid hormone (PTH) inhibit HCO3- absorption by the rat medullary thick ascending limb (MTAL). Studies were performed on rat MTAL tubule suspension to specify the H(+)-HCO3- membrane transporters affected by these hormones and the implicated intracellular second messengers. Arginine vasopressin (AVP) and PTH stimulated cell adenosine 3',5'-cyclic monophosphate (cAMP) production with a relative rank order potency of AVP > rat PTH-(1-34) > bovine PTH-(1-84). Significant cell acidification in HCO3- -CO2-free medium, monitored in 2'7'-bis(carboxyethyl)-5(6')-carboxyfluorescein-loaded cells, was caused by 0.1 nM AVP, 1 nM rat PTH-(1-34), but not by < 100 nM bovine PTH-(1-84), as well as by 10(-4) M 8-bromo-cAMP and 2 x 10(-5) M forskolin; 10 nM AVP or rat PTH-(1-34) did not alter the intracellular pH when Na+/H+ antiport was inhibited by 2 mM amiloride. Prostaglandin E2 (PGE2, 10(-6) M), which inhibited AVP-stimulated cell cAMP production, reduced by 35% the cell acidification response to 10 nM AVP. AVP and 8-bromo-cAMP inhibited Na+/H+ antiport-dependent cell pH recovery from intracellular acidification, which was explained by a decrease in the Vmax of the antiporter. AVP did not directly affect K(+)-HCO3- cotransport and plasma membrane H(+)-ATPase of rat MTAL cells. Cytosolic calcium ([Ca2+]i), monitored in fura-2-loaded cells, was unaffected by up to 1 nM AVP, 100 nM PTH, glucagon, calcitonin, and oxytocin, and 1 microM PGE2; however, 100 nM AVP, but not 1-desamino-8-D-AVP (dDAVP), caused a peak increase in [Ca2+]i, even in the absence of extracellular Ca2+, and stimulated cell accumulation of [3H]inositol phosphates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:cAMP-dependent control of Na+/H+ antiport by AVP, PTH, and PGE2 in rat medullary thick ascending limb cells. 838 52

There is considerable evidence that the central nervous system (CNS) is significantly involved in potassium homeostasis: (a) Potassium-specific receptors located in the liver or hepatic portal circulation initiate a reflex increase in potassium excretion via vagal afferents. This reflex is lost or diminished with hypophysectomy. (b) Oscillators, presumably located in the hypothalamus, determine a circadian rhythm in the renal excretion of potassium. The efferent control factors are unknown. (c) Exogenous hypophysial peptides (vasopressin, oxytocin, and alpha-, beta-, and gamma-MSH) stimulate increased potassium (and sodium) excretion. (d) Hypophysial gamma-MSH or a related hypophysial peptide stimulates an increase in the excretion of potassium (and sodium) following uninephrectomy in the rat. This adaptive response involves cerebral, naloxone-inhibitable opioid receptors. (e) Intra-third-ventricular infusion of hypertonic NaCl initiates an increased potassium (and sodium) excretion through undetermined humoral mechanisms and is blocked by prior hypophysectomy. (f) In rats depleted of potassium by low potassium intake or by production of DOCA hypertension, an inhibition of skeletal muscle Na+, K(+)-ATPase ion pump activity is directed by hypothalamic centers and involves inhibition by alpha-adrenergic activity of slow twitch fibers and inhibition by undetermined humoral factors of fast twitch fibers. (g) Potassium receptors, either demonstrated or inferred, initiate reflex increases in respiration, heart rate, blood pressure, and peripheral tissue potassium uptake as well as a reflex inhibition of skeletal muscle ion pumps. (h) Evidence for CNS regulation of potassium intake is equivocal. Major gaps exist in this emerging picture of neuroendocrine involvement in potassium homeostasis.
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PMID:The central nervous system in potassium homeostasis. 847 70

Occupancy of oxytocin receptor (OTR) binding sites in pregnant rat myometrial membranes with iodinated oxytocin antagonist (OTA), followed by detergent solubilization and size selection, showed that radioactivity eluted in two distinct peaks: one corresponding in size to the isolated receptor (approximately 60 kDa) and the other ranging from 240 to 320 kDa. The unliganded 240- to 320-kDa fraction contained OTRs coupled to G proteins, as the addition of oxytocin (OT) increased guanosine 35S-labeled 5'-O-(3-thiotriphosphate) binding up to twofold in a dose-dependent manner. The effects of OT were blocked by coincubation with OTA. G protein alpha-subunits associated with OTRs in the 240- to 320-kDa peak were identified by immunoadsorption. Significant amounts of both G alpha q/11 and G alpha i3 were associated with the OTR; a lesser amount of G alpha s was complexed. Using the same approach but with antibodies to effector enzymes, we observed that phospholipase C beta 1 (PLC beta 1) and PLA2 were also associated with the OTR. The results corroborate the well-established interaction of OTR with Gq and further show that Gi coupling might be an important component of OTR signal transduction. To further investigate the interaction of Gi with the OTR, we showed that OT stimulation of guanosine 5'-triphosphatase activity in intact myometrial membranes was inhibited by pertussis toxin. Pertussis toxin-stimulated ADP ribosylation of G alpha i in myometrial membranes was also decreased by OT treatment. These findings with pertussis toxin strongly indicate that OTR is coupled to Gi in rat myometrial membranes. The 60-kDa OTR peak (noncoupled receptor) was demonstrable in the myometrium only before the end of gestation and after parturition and accounted for about one-half the 125I-OTA binding activity. At term, there was about a fivefold increase in binding and almost a complete shift to the 240- to 320-kDa-size complex. Thus the established increased sensitivity of the myometrium to OT at term could be the result of both upregulation of OTRs and an increase in the fraction of receptors coupled to signal transduction components, one of which is Gi.
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PMID:Coupling of oxytocin receptor to G proteins in rat myometrium during labor: Gi receptor interaction. 917 88

The objective of these experiments was to determine the role of Ca2+ during oxytocin-stimulated prostaglandin (PG) F2 alpha release from bovine endometrial tissue in vitro. Uteri were collected from dairy cows on the day after spontaneous luteal regression. Caruncular endometrial explants were dissected and incubated in vitro to determine phospholipase C activity or PGF2 alpha release. A23,187 (a calcium ionophore) and maitotoxin (an activator of voltage-gated L-type calcium channels) stimulated release of PGF 2 alpha in a concentration-dependent manner (P < 0.05). Thapsigargin (induces accumulation of Ca2+ in the cytoplasm by inhibiting endoplasmic reticulum Ca2+/ATPase pumps) stimulated release of PGF2 alpha in a concentration-dependent manner as well (P < 0.13). Oxytocin (10(-6) M), AIF4- (a nonspecific activator of G-proteins; 10(-5) M), A23,187 (10(-5) M), and melittin (a stimulator of phospholipase A2; 10(-4) M) stimulated PGF2 alpha release when explants were incubated in Ca(2+)-free medium (P < 0.10); however, oxytocin, A23,187, or melittin were unable to stimulate PGF2 alpha release when explants were incubated in Ca(2+)-free medium containing the calcium chelator EGTA (P < 0.10). This treatment did not prevent oxytocin or AIF4- from stimulating phospholipase C activity (P < 0.08). CoCl2 (a nonspecific Ca2+ channel blocker) and methoxyverapamil (a specific voltage-gated L-type Ca2+ channel blocker) prevented oxytocin from stimulating PGF2 alpha release (P < 0.05). Our results suggest that both extracellular and intracellular Ca2+ may be required for oxytocin to stimulate PGF2 alpha secretion in bovine endometrial tissue.
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PMID:Cellular mechanisms by which oxytocin mediates uterine prostaglandin F2 alpha synthesis in bovine endometrium: role of calcium. 986 39

The molecular recognition hypothesis for peptides is that binding sites of ligands and their receptors are encoded by short, complementary segments of DNA. A corollary hypothesis for nonpeptide ligands posited here is that peptide replicas may be encoded by the DNA segment complementary to the receptor binding sites for nonpeptides. This corollary was tested for digitalis. a family of cardiotonic and natriuretic steroids including ouabain. A hexapeptide (ouabain-like peptide, OLP) complementary to a ouabain binding site on sodium potassium dependent adenosine triphosphatase (Na+ K+ ATPase) exhibited activity in a digitalis bioassay. Antisera to the complementary peptide (OLP) stained the neurohypophysis in an immunocytochemical procedure. The complementary peptide was found to share an identical 4-amino acid region with the 39-amino acid glycopeptide moiety of the vasopressin-neurophysin precursor. This glycopeptide was isolated from pituitary extracts; it exhibited digitalis-like activity in the submicromolar range and cross-reacted with complementary peptide antibodies. Another digitalis-like substance with high activity also was detected in the extracts. These results demonstrate that the vasopressin-neurophysin glycopeptide has digitalis-like activity. Moreover, the findings are consistent with the hypothesis that peptide mimetics of nonpeptides are encoded in the genome.
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PMID:A molecular recognition hypothesis for nonpeptides: Na+ K+ ATPase and endogenous digitalis-like peptides. 1035 21


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