Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The initiation of human parturition remains an enigma but is thought to involve a number of hormonal signals such as oxytocin and prostaglandins. One other possible signal is placentally derived corticotropin-releasing hormone (CRH). We have recently reported that the human myometrium expresses a specific receptor for CRH which changes to a high affinity state prior to term. In view of this we sought to determine whether this receptor is functionally linked to some of the known modulators of myometrial function. Myometrial membranes were prepared by differential centrifugation from either pregnant (caesarian section) or non-pregnant (hysterectomy) myometrium. For binding studies the membranes were incubated with radiolabelled oCRH at 22 degrees C for 2 h. For second messenger studies they were incubated at 37 degrees C for 10 or 30 min with either 0.5 mM ATP and 10 mM theophylline (cAMP) or 0.05 mM arachidonic acid or 0.5 mM linoleic acid (PGE2). When increasing concentrations of membranes were incubated with radiolabelled oCRH an interesting phenomenon was observed. In non-pregnant membranes the binding reached a plateau, whereas in membranes prepared from pregnant myometrium, the binding decreased at concentrations above 130 micrograms/ml. Possible explanations for this phenomenon include an inhibitor which prevents ligand-receptor binding or an enzyme which destroys the receptor binding region of the ligand. Incubation of both types of membranes with GTP or its analogue, GppNHp, resulted in a dose-dependent inhibition of specific binding suggesting that the myometrial CRH receptor is linked to a G regulatory protein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The human myometrial CRH receptor: G proteins and second messengers. 820 32

Effect of oxytocin on contractile activity, passive and Mg2+, ATP-dependent Ca2+ transport through myocyte plasmic membrane was studied in the experiments carried out on intact samples of the uterus smooth muscle and fraction of myometrium sarcolemma vesicules. It was shown that at short-term (30 s) application of oxytocin (2.10(-7) M) powerful prolonged contractile reaction of myometrium bands was observed. After the chelating of Ca2+ in the washing medium by means of EGTA (2mM) or while introducing into it blockers of electrically controlled calcium channels the bands responded to oxytocin application with a single physical contraction. High concentrations of peptide hormone (10(-6) M) introduced into the preincubation medium of the smooth muscle bands before the isolation of the membrane fraction or directly into the incubation medium produced no effect on passive liberation of Ca2+ vesicules from the sarcolemma vesicules. At the same time preincubation of the bands in the solution containing smaller concentration of octapeptide (10(-7) M) decreased the initial velocity of Mg2+, ATP-dependent Ca2+ transport in the vesicules by 30% on the average. Possible mechanisms of oxytocin effects on intracellular homeostasis of Ca2+ in the myometrium, on the contractile activity of the uterus are discussed.
 ...
PMID:[Uterotonic effect of oxytocin and transport of Ca2+ through the myometrial sarcolemma]. 847 40

Agents previously implicated in control of the hypothalamo-pituitary-gonadal axis were screened for their ability to regulate male rat gonadotropes directly. GnRH-evoked gonadotropin release is accompanied by oscillations of intracellular Ca2+ concentration ([Ca2+]i) and of an outward K+ current that is activated by Ca2+. Substances that caused current responses similar to those with GnRH were hypothesized to evoke secretion. Endothelin-1, oxytocin, neurotensin, pituitary adenylate cyclase-activating polypeptide, and serotonin raised [Ca2+]i and evoked LH release as assayed by the reverse hemolytic plaque assay. These agents affected only subpopulations of gonadotropes establishing functional heterogeneity of pituitary gonadotropes. One neuromodulator (ATP) evoked ionic current in all gonadotropes but the current was different than that evoked by GnRH. Many other substances, including galanin and neuropeptide Y, caused no changes in currents and were considered not to affect [Ca2+]i and not to be secretagogues for gonadotropes.
 ...
PMID:Functional heterogeneity of pituitary gonadotropes in response to a variety of neuromodulators. 896 Dec 53

It was shown that oxytocin (OT) elicits electrophysiological responses in cultured monolayers of NCL-SG3, a human immortalized sweat gland cell line. The response to OT was greater for basal applications. It was also found that monolayers respond to ATP with a transient transepithelial-potential change, with a more pronounced response to apical than to basal applications. The IC50 for the response to OT was 180 nM at room temperature. The response to OT was not due to effects of OT on vasopressin (AVP) receptors as evidenced by three tests: (a) The response was completely blocked by the selective OT-receptor antagonist [Mpa1,D-Tyr(Et)2,Thr4,Orn8]-OT (CAP) applied at equal concentrations (100-1000 nM) to that of OT. (b) The response to OT was similar to that of ionomycin (2 microM) or ATP (150 microM). In contrast, the response to AVP (500 nM) or cAMP (2 mM) were smaller and of a different time course. (c) OT increased but AVP had no effect on the intracellular free calcium. It is suggested that OT may have a role in the regulation of salt balance in sweating.
 ...
PMID:Electrophysiological responses to oxytocin and ATP in monolayers of a human sweat gland cell line. 916 54

Uterotonic peptide hormone oxytocin has been studied for its effect on ATP-dependent accumulation of Ca2+ nonsensitive to the effect of ruthenium red (10 microM) that is potentiated by Ca2+-precipitating anion - oxalate. That was studied in experiments made on the suspension of myometrium cells from estrogenized rats processed by digitonin (0.1 mg/ml) with the aim permeabilization of plasmatic membrane. The preliminary processing of intact myocytes by oxytocin solution (final concentration 100 mM) to permeabilization of plasmatic membrane causes partial inhibition (stimulated by oxalate by 25-30% (0-10 mM) of Mg2+, ATP-dependent accumulation of Ca2+ in nonmitochondrion intracellular calcium depot of perforates smooth-muscled cells. The value of the component of power-dependent accumulation of Ca2+, that is inhibited by oxytocin, increased with both the incubation time and oxalate concentration. Thapsigargin and cyclopiasonium acid, selective inhibitors of calcium pump of endo(sarco)plasmatic reticulum, when used in saturation concentration (50 mM and 10 mM, respectively), completely inhibit the component of Mg2+, ATP-dependent accumulation of Ca2+ in nonmitochondrial intracellular calcium depot that is stimulated with oxalate (< 10 mM) and inhibited with oxytocin (100 mM). It is concluded that oxytocin partially inhibits Mg2+, ATP-dependent calcium pump of myometrium cell endoplasmic reticulum.
 ...
PMID:[Treatment of intact myometrial cells with oxytocin inhibits Mg2+, ATP-dependent accumulation of Ca2+ in endoplasmic reticulum]. 922 49

1. Glibenclamide, a blocker of ATP-sensitive potassium channels, has been shown to antagonize relaxin as a uterine relaxant in the rat in vivo but not in vitro. The aim, therefore, was to investigate whether the discrepancy between the two studies was a consequence of differences in (1) muscle layers, (2) hormonal conditions or (3) spasmogens utilized. Relaxin was compared with salbutamol and levcromakalim. 2. Relaxin was of similar potency as a uterine relaxant against oxytocin (0.2 mM)-induced spasm with tension measured in the circular or longitudinal muscle layers. Glibenclamide (10 microM) did not antagonize relaxin or salbutamol in these preparations but greatly antagonized levcromakalim (91-fold). Relaxin was a relaxant of tension activated by transmural electrical stimulation in uteri from rats that had been ovariectomized, although the maximal effect was only 30 +/- 15%, and in uteri from rats that had been treated with 17 beta-estradiol benzoate. Glibenclamide was not an antagonist of relaxin in the latter preparation but did antagonize levcromakalim (118-fold). Relaxin also inhibited spontaneous phasic tension development in uteri from ovariectomized rats but again was not antagonized by glibenclamide. 3. Because relaxin was not antagonized by glibenclamide under any of these various conditions, it would appear that the in vivo-in vitro discrepancy in the antagonism of relaxin by glibenclamide is not attributable to the effects of different muscle layers, hormonal conditions or spasmogens. It may be that the mechanism of action of relaxin or glibenclamide or both differs between in vivo and in vitro preparations.
 ...
PMID:Relaxin as a relaxant of the isolated rat uterus: comparison with its mechanism of action in vivo. 934 34

Mammary myoepithelial cells were isolated and cultured to characterize their properties. The intracellular calcium concentration (Cai2+) was measured using the ratio of fura-2 fluorescence at 340 nm to that at 360 nm (F340/F360), and the contraction was simultaneously monitored by the change of fluorescence intensity at 360 nm (F360). Cultured myoepithelial cells retained their contractile machinery as in the intact tissue. NBD-phallacidin fluorescence, which marks F-actin, and electron microscopy showed abundant bundles of microfilaments in the cytoplasm. Oxytocin (> 0.1 nM) induced an increase in Cai2+ and contraction. The amplitude and time course of the Cai2+ increase were not markedly affected in the Ca2+-free solution. Nifedipine (10 microM) did not affect the response to oxytocin. ATP (>1 microM) induced an increase in Cai2+ and contraction. The response to ATP was not affected by Ca2+ removal, but was suppressed by suramin (100 microM), an antagonist of P2-purinergic receptors. The order of potency of nucleotides to increase Cai2+ was ATP = ADP > UTP > UDP. These findings indicate the presence of P2-purinergic receptors in mammary myoepithelial cells. The results suggest that stimulant-induced Cai2+ increases and contractions are due to release of Ca2+ from intracellular stores in these cells. In addition to the hormonal action of oxytocin, extracellular nucleotides may function as paracrine agents to contract myoepithelial cells in the mammary gland.
 ...
PMID:Involvement of P2-purinergic receptors in intracellular Ca2+ responses and the contraction of mammary myoepithelial cells. 935 97

The effect of the nonionic detergent digitonin on ruthenium red-insensitive, oxalate-stimulated, and thapsigargin-suppressed accumulation of Ca2+ by suspension of myometrial cells from ATP- and Mg(2+)-containing incubation medium was studied using passive loading with 45Ca2+. The dependence of Ca2+ accumulation by the cells on the concentration of digitonin is bell-shaped, the maximal Ca2+ uptake being observed at 0.05-0.1 mg/ml digitonin. Myocytes chemically skinned with digitonin represent a suitable experimental model for studying kinetic properties of the uterine myocyte endoplasmic reticulum Mg2+, ATP-dependent Ca2+ pump and assessing sensitivity of this Ca(2+)-transporting system to various effectors including the uterotonic octapeptide oxytocin.
 ...
PMID:Suspension of smooth muscle cells treated with digitonin as a model for studying the myometrial endoplasmic reticulum calcium pump. 948 75

Conditioned fear stimuli suppress motor activity. The fear stimuli suppress vasopressin and facilitate oxytocin and prolactin release. These fear responses are impaired by selective destruction of noradrenergic neurones. Adenosine 5'-triphosphate is co-released from noradrenergic nerve terminals with noradrenaline. Thus the possibility arises that the behavioural and neuroendocrine responses may be mediated by purinergic rather than noradrenergic synapses. We examined whether suramin, an inhibitor of P2 and NMDA receptors, blocks conditioned fear responses. Suramin injected i.c.v. 30 min before testing stimuli impaired conditioned fear responses. The role of purinergic P2 receptors in expression of the behavioural and neuroendocrine responses to conditioned fear stimuli is discussed.
 ...
PMID:Effects of suramin on neuroendocrine and behavioural responses to conditioned fear stimuli. 960 56

The regulation of transport of the fluorescent organic cation 4-(4-dimethylaminostyryl)-N-methylpyridinium (ASP+) by renal proximal tubular organic cation transport was studied in IHKE-1 and LLC-PK1 cells with a recently established fluorometric technique (Stachon et al., 1996, 1997). Stimulation of Ca++/diacylglycerol-dependent protein kinase by 1,2-dioctanoyl glycerol (DOG; 0.01-1 mumol/l, n = 7), ATP (0.1 mmol/l, n = 9), oxytocin (0.1 mumol/l, n = 6) and bradykinin (1 mumol/l, n = 7) resulted in an increase of ASP+ accumulation in IHKE-1 cells by 35 +/- 9% (DOG), 65 +/- 30% (ATP), 66 +/- 14% (bradykinin) and 70 +/- 20% (oxytocin) as compared with basal conditions, whereas ASP+ accumulation was slightly reduced in LLC-PK1 cells after stimulation with DOG (1 mumol/l, -20 +/- 7%, n = 10) and angiotensin II (0.1 nmol/l, -20 +/- 5%, n = 6). ASP+ accumulation in IHKE-1 cells also was increased by 0.5 mumol/l (20 +/- 8%, n = 8) and 1 mumol/l forskolin (35 +/- 13%, n = 19), and by 8-bromo-cAMP (1 mumol/l, 125 +/- 25%, n = 9), both activators of the cAMP-dependent protein kinase (PKA). Activation of the cGMP-dependent protein kinase (PKG) by human atrial natriuretic peptide (10 nmol/l, n = 10) or 8-bromo-cGMP (0.1 mmol/l, n = 12) resulted in an increase of 35 +/- 5% and 28 +/- 6%, respectively. Activation of PKA and PKG had no influence on ASP+ transport in LLC-PK1 cells. Regulation of ASP+ uptake by these two cell lines may be caused by direct phosphorylation of the organic cation transporters involved or by regulation of trafficking of the transporters to the membrane. Differences in the organic cation transporter isoforms or alternatively, in the trafficking may contribute to the distinct regulation of ASP+ transport in IHKE-1 and LLC-PK1 cells.
 ...
PMID:Regulation of organic cation transport in IHKE-1 and LLC-PK1 cells. Fluorometric studies with 4-(4-dimethylaminostyryl)-N-methylpyridinium. 965 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>