UNIPROT:P01178 - FACTA Search

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Query: UNIPROT:P01178 (oxytocin)
15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detection of the neurohypophysial hormones vasopressin (AVP) and oxytocin (OT) in the testis of several species has led to the proposal that these peptides may have a physiological role in the regulation of testicular function. Therefore, we investigated whether the contractile myoid cells of rat seminiferous tubules express functional receptors for AVP or OT and, thus, constitute a target for these hormones. This study used primary cultures of purified peritubular myoid cells derived from rats both before and after puberty. By several criteria, myoid cells prepared from adult rats expressed vasopressin receptors (VPRs). We detected specific and saturable [3H]AVP binding to a single population of sites with a Kd of 7.5 nM and a binding capacity of 145 fmol/mg protein. AVP stimulated the accumulation of inositol phosphates in a dose-dependent manner with an EC50 of 1.7 nM. Cloning and sequencing of the myoid cell VPR confirmed it to be the V1a subtype of VPR. VPR expression by myoid cells is under developmental control, as the receptors are present in the adult rat, but absent before puberty. In contrast, OT receptors were not expressed at any stage of development. Peritubular myoid cells are also responsive to endothelin-1 (ET-1), which potently stimulated phosphoinositidase-C. However, unlike AVP, the ET-1 responses were observed both before and after sexual maturity, suggesting different roles for AVP and ET-1 in the control of myoid cell function. Our data establish that the myoid cells of the adult rat seminiferous tubule are a target for AVP. This indicates an additional role for AVP in the regulation of testicular function and male fertility in the adult rat.
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PMID:Rat testicular myoid cells express vasopressin receptors: receptor structure, signal transduction, and developmental regulation. 753 65

The objectives of this study were to evaluate and compare the actions of endothelin-1 (ET-1), oxytocin, prostaglandin F2 alpha (PGF2 alpha) and inositol 1,4,5-trisphosphate (IP3) on 45Ca2+ mobilization in permeabilized rat myometrial cells and to examine the activation of the inositol lipid cycle in intact myocytes. Cells were isolated from late pregnant rat myometrium and used as confluent monolayers after a single passage. All four agonists caused a biphasic release of 45Ca2+ from non-mitochondrial pool(s), with the rank order of potency: oxytocin > PGF2 alpha > ET-1 > IP3. Inhibitors of phospholipase C blocked ET-1- and oxytocin-promoted but not PGF2 alpha-promoted 45Ca2+ efflux. Similarly, heparin, an IP3 receptor blocker, failed to inhibit PGF2 alpha-induced 45Ca2+ release while inhibiting the action of the other agonists. Endothelin-1 and oxytocin stimulated inositol phosphate accumulation at concentrations similar to those that promoted 45Ca2+ efflux, whereas about 100 times higher concentrations of PGF2 alpha were needed to activate this signaling pathway in intact cells. It is concluded that the primary action of PGF2 alpha in myometrial cells is to enhance Ca2+ influx, whereas oxytocin and ET-1 receptors are coupled to phospholipase C, generating IP3 and raising the intracellular concentration of free Ca2+ from intracellular as well as extracellular sources.
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PMID:Signal transduction in rat myometrial cells: comparison of the actions of endothelin-1, oxytocin and prostaglandin F2 alpha. 758 72

The mechanical effects of KCl, oxytocin and endothelin-1 on pregnant rat myometrium were examined using intact strips and beta-escin-treated skinned strips. Myometrial tissues from delivering rats were more sensitive to 10.7 mM K+ compared to mid and late gestation. Maximum contractions induced by K+ were obtained at concentrations of 118 mM at mid and late gestation and during delivery. The maximum amplitude of contractions induced by oxytocin and endothelin-1 compared to the 118 mM K(+)-induced contraction increased during the progress of gestation. Maximum contractions induced by oxytocin and endothelin-1 were greater than those induced by 118 mM K+ at delivery, and maximum contractions by oxytocin were larger than those by endothelin-1 during delivery. In 10 microM nifedipine and Ca(2+)-free (containing 2 mM EGTA) solutions, 118 mM K+ contractions were completely abolished; however, both oxytocin and endothelin-1 produced contractions. In Ca(2+)-free solutions, contractions by oxytocin were larger than those by endothelin-1. In skinned myometrial strips, guanosine 5'-O-thiotriphosphate (GTP, 1 microM-1 mM), guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S, 0.1-100 microM) and oxytocin (1 nM-0.1 microM) with 10 microM GTP, but not endothelin-1 with 10 microM GTP increased Ca2+ sensitivity of contractile force.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gestational changes in oxytocin- and endothelin-1-induced contractility of pregnant rat myometrium. 758 54

Present knowledge allows the identification of some features of the initiation of human parturition. Progesterone reduces myometrial sensitivity to labour-inducing agents. It suppresses gap junction formation and facilitates beta-adrenergic receptor expression by the myometrium which, in turn, exerts a positive feedback by enhancing beta-adrenergic-induced increases in placental progesterone production. Inhibition of gestagen action does not result in immediate initiation of labor but sensitises myometrial cells to contraction-inducing agents. Estrogens, in contrast, enable the myometrium to prepare for parturition by inducing oxytocin receptors and this seems to be the first step towards parturition. Coordinated myometrial contractions are facilitated by the increased gap junctions due to the estrogen drive. Absence of estrogen will result in failed parturition. The myometrium seems to be sensitised to oxytocin by placental CRF. Myometrial CRF receptors increase their avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety of auto- and paracrine events which culminate in increased free intracellular calcium and the consequent contractions. In this cascade, prostaglandins can be identified as positive feedback agents, as they further enhance estrogen-induced expression of oxytocin receptors. Another second messenger of oxytocin action are the inositol phosphates which can further increase free intracellular calcium concentrations. Finally, endothelin-1, derived from endometrium and decidua, under oxytocin control, may serve as a myometrial contractor following delivery when oxytocin concentrations decline but when a strong myometrial contraction is needed to prevent large blood loss during and after placenta expulsion.
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PMID:Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human. 799 41

Mouse uterine horns from 4 states (estrogen-primed and early-, mid-, and late-pregnancy) were used to study the effect of endothelin-1 (ET) vs carboprost (Car) and oxytocin (Oxy). In K(+)-Krebs (KCl 40 mmol.L-1) solution, ET (1-300 nmol.L-1), Car (0.002-20 mumol.L-1), and Oxy (0.6-60 nmol.L-1) evoked concentration-dependent increases in tension of the uterine horns from 4 different states. Emax for ET were 1.12 +/- 0.26, 1.27 +/- 0.18, and 1.49 +/- 0.13 g in early-, mid-, and late-pregnancies, respectively. Emax for Car in mid- was twice that in late-pregnancy, whereas Emax for Oxy in late- was thrice that in mid-pregnancy. EC50 for ET were 9.6, 5.8, and 6.3 nmol.L-1 in early-, mid-, and late-pregnancies, respectively, and were only 2% to 7% of that for Car and 3-15 times of that for Oxy in various gravid stages. The results suggest that the contractile activity of pregnant mouse uterus to ET is more potent than that of Car while slightly weaker than that of Oxy.
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PMID:Effects of endothelin-1 on isolated uterine horns in estrogen-primed and pregnant mice. 801 Jan 5

This investigation was conducted to evaluate the potential capacity of the human fetal membranes-decidua parietalis, and in particular the chorion laeve, to degrade uterotonins that are produced in amnion, are present in amniotic fluid, or both. The four uterotonins that have been evaluated most frequently as myometrial contractants potentially involved in the initiation of human parturition are prostaglandins, oxytocin, endothelin-1, and platelet-activating factor. We assessed the levels of mRNA and the specific activities (SAs) of enkephalinase (the plasma membrane endopeptidase that degrades endothelins) and prostaglandin dehydrogenase (PGDH) in human fetal membranes, i.e. amnion and chorion leave, and in decidua parietalis. The SA of oxytocinase (which inactivates oxytocin) in these tissues also was determined. The SA of enkephalinase in chorion laeve from all anatomical sites (singleton and diamnionic-dichorionic twin placentae) in all pregnancies studied (mean +/- SEM, 95 +/- 7.9 ng/min.mg protein; n = 28) is similar to that in human fetal kidney (89.5 +/- 2.8; n = 6). Kidney tissue is believed to be one of the richest sources of enkephalinase. The SAs of enkephalinase in amnion (18.3 +/- 2.3 nmol/min.mg protein; n = 29) and in decidua parietalis (31.8 +/- 6.7; n = 20) also were high, but significantly less than that in chorion leave. The level of enkephalinase mRNA in chorion laeve in singleton pregnancies is high, as is the SA of enkephalinase (111.9 +/- 10.6 nmol/min.mg protein; n = 17). In paired chorion laeve tissues from five diamnionic-dichorionic twin placentae, the SAs of enkephalinase in reflected chorion laeve (74 +/- 12.8; P < 0.06 compared with singletons) and fused chorion laeve (64.8 +/- 6.5; P < 0.001 compared with singletons) were similar. The SA of PGDH in reflected chorion leave (46.3 +/- 6.9 nmol/min.mg protein; n = 19) was significantly greater than that in decidua (16 +/- 5.5; n = 15). There was a significant correlation between the levels of PGDH mRNA and PGDH enzyme SA. In fused chorion laeve of diamnionic-dichorionic twin placentae, the SA of PGDH (14.9 +/- 7.3; n = 4) was much less than that in reflected chorion laeve of the same twin pregnancy (70.5 +/- 14.7; n = 4). PGDH mRNA was not detectable in amnion tissue (n = 5) by northern analysis, and the SA of PGDH (< 1.2 +/- 1.0; n = 6) in amnion was undetectable or near the lower limit of assay detection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human fetal membrane contribution to the prevention of parturition: uterotonin degradation. 810 36

The presence of a phosphoramidon-sensitive endothelin-1-converting enzyme was investigated in the rat isolated uterus. Endothelin-1 and its precursor, big-endothelin-1, increased the rate of spontaneous contractions and caused tonic contractions. Responses to big-endothelin-1 had a slower start than those to endothelin-1. The tonic contraction induced by big-endothelin-1 (10 nM) was nearly abolished by phosphoramidon (100 microM), but the response to an equieffective concentration of endothelin-1 (3 nM) was not affected. Big-endothelin-1 (EC50 6.7 nM) was only 7-fold less potent than endothelin-1 (EC50 0.9 nM), whereas endothelin-3 was much less potent (EC50 > 100 nM). The endothelin ETA receptor antagonist, BQ-123 (40, 150 and 600 nM), induced graded rightward shifts of the concentration-response curve for endothelin-1. Schild analysis yielded a straight line with a slope not different from unity, and a pA2 value of 7.76. At 100 nM, BQ-123 specifically blocked responses to both endothelin-1 (3 nM) and big-endothelin-1 (10 nM), without modifying those to oxytocin (5 nM), acetylcholine (3 microM) or bradykinin (0.5 nM). Our results suggest the presence of phosphoramidon-sensitive endothelin-converting enzyme and demonstrate the occurrence of functional endothelin ETA receptors in the rat uterus.
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PMID:Big-endothelin-1 contracts rat isolated uterus via a phosphoramidon-sensitive endothelin ETA receptor-mediated mechanism. 824 32

The impact of insulin-like growth factor-I (IGF-I) basic fibroblast growth factor (bFGF), endothelin-1 (ET-1), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF-alpha) and platelet-derived growth factor (PDGF) on the release of progesterone (P4) and oxytocin (OT) from individual bovine corpora lutea at different stages of the oestrous cycle and pregnancy was evaluated with a microdialysis system (MDS) in vitro. IGF-I (1 microgram mL-1) induced significantly the acute effects on P4 release at the late luteal stage (Days 15-18) and early pregnancy (Days 60-120), whereas bFGF (100 ng mL-1) was extremely effective in stimulating P4 release particularly during the mid-luteal stage (Days 8-12). Both peptides stimulated (P < 0.05) the release of OT throughout the three luteal stages and during early and late pregnancy (Days 30-60 and Days 150-210). ET-1 (100 ng mL-1) clearly inhibited P4 release during the early (Days 5-7) and mid-luteal phase and stimulated OT release only during the mid-luteal stage (P < 0.001). TNF-alpha (100 ng mL-1) stimulated the release of P4 exclusively at the early luteal phase (P < 0.05), whereas OT secretion was increased by TNF-alpha during all stages of the oestrous cycle (P < 0.001). TGF-alpha and PDGF (100 ng mL-1) were effective in stimulating P4 release particularly during late pregnancy (P < 0.05). In contrast, stimulation of OT secretion by TGF-alpha was maximal during the late-luteal stage (P < 0.001), whereas PDGF significantly increased OT secretion during the oestrous cycle (except the early luteal stage) and pregnancy (P < 0.001). The data demonstrate distinct and stage-specific effects of growth factors on P4 and OT secretion in vitro. IGF-I, bFGF and TGF-alpha may play an important role in corpus luteum (CL) function during the oestrous cycle and pregnancy since they are locally expressed and synthesized, there are receptors for these growth factors, and they have been demonstrated to exert biological effects on the CL.
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PMID:Effects of local growth factors on the secretory function of bovine corpus luteum during the oestrous cycle and pregnancy in vitro. 889 36

Prostaglandin F2alpha (PGF2alpha) has been recognized as the physiological luteolysin in ruminants and other species for more than three decades; however, the mechanisms involved in its action are poorly understood. We previously have shown that endothelin-1 (ET-1) mediates, at least in part, the action of PGF2alpha, and the current study examines the effect of PGF2alpha on the expression of ET-1 in bovine corpus luteum (CL). Endothelins (ETs) were extracted from CL, collected at various times of the estrous cycle, and highest levels were found during luteolysis. The expression of prepro-ET-1 was also highest in regressing CL, suggesting that PGF2alpha may have elevated ET-1 expression. This was confirmed by demonstrating that administration of PGF2alpha to heifers at midcycle elevated luteal ET-1 expression. Levels were induced as soon as 2 h after PGF2alpha treatment and 24 h later were 7-fold higher than preinjection levels. Endothelial cells isolated from bovine CL produced ET-1, and addition of PGF2alpha, oxytocin (OT), and vasopressin-augmented ET biosynthesis. Induction of ET-1 expression by PGF2alpha in these cells was evident after a short incubation time (15-90 min). Taken together, these data suggest that stimulation of luteal ET-1 expression by PGF2alpha may be achieved by several nonmutually exclusive mechanisms: 1) by acting directly on luteal endothelial cells; 2) indirectly, via OT release from large luteal cells; and 3) by causing hypoxia in the CL (as a result of ET-1-induced vasoconstriction). The latter mechanism may serve to augment ET-1 secretion in a positive-feedback process.
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PMID:Regulation of endothelin-1 expression in the bovine corpus luteum: elevation by prostaglandin F 2 alpha. 894 Mar 33

Prostaglandin F2 alpha (PGF2 alpha) is a primary luteolysin in the cow. Although the mechanisms involved in luteolysis are thought to be a complex of its direct action on luteal cells and indirect effect on luteal blood flow, the detailed mechanisms remain to be elucidated. This study focuses on the possible interaction of endothelial cells-derived endothelin-1 (ET-1) with PGF2 alpha in the rapid suppression of progesterone release from the bovine corpus luteum (CL). In in vitro microdialysis system (MDS) of CL, PGF2 alpha acutely stimulated the release of progesterone and oxytocin during infusion and ET-1 release after infusion. Moreover, PGF2 alpha induced slight decrease of progesterone release during the last period of the experiment (8-11 h after PGF2 alpha exposure). Two 1 h-perfusions of ET-1 at 3 h intervals induced only a slight decrease of progesterone release after the second perfusion. This treatment also affected the oxytocin release; the first ET-1 perfusion produced an acute stimulation, whereas the second ET-1 perfusion inhibited the release to below 50%. When the CL pieces were pre-perfused with PGF2 alpha for 2 h, the two consecutive perfusion of ET-1 at 3 h intervals induced drastic decrease in progesterone and oxytocin release only after the second ET-1 perfusion. Thus, a pre-exposure with PGF2 alpha clearly potentiated the inhibiting activity of ET-1 in the progesterone release. These results suggest a physiological impact of PGF2 alpha and ET-1 in the rapid cascade of functional luteolysis in vivo, and a possible interaction between endothelial cells and luteal cells.
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PMID:Prostaglandin F2 alpha promotes the inhibitory action of endothelin-1 on the bovine luteal function in vitro. 907 91

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