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)

Madin-Darby canine kidney (MDCK) cells grown in tissue culture have the morphological properties of distal tubular epithelial cells, form tight junctions, and lack several proximal tubular enzyme markers. Adenylate cyclase in these cells was stimulated by vasopressin, oxytocin, prostaglandins E1 and E2, glucagon, and cholera toxin. Hormone-stimulated adenylate cyclase activity in isolated membrane preparations was dependent on low concentrations of GTP and had the MgCl2 and pH optima expected for the kidney enzyme. The results, as well as the demonstration of enhanced hemicyst formation induced by cyclic AMP, suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cell of origin. When MDCK cells were injected into baby nude mice, continuous nodule growth was observed until adulthood was attained. Histological studies revealed the presence of two cell types: normal mouse fibroblasts which comprise 80--90% of the solid nodule mass, and MDCK cells, which formed epithelial sheets lining internal fluid-filled glands. Electron microscope analysis showed that the mucosal surfaces of the cells were characterized by microvilli which faced the lumen of the glands, that adjacent MDCK cells were joined by tight junctions, and that the serosal surfaces of the epithelial sheets were characterized by smooth plasma membranes which were lined by a continuous basement membrane. These observations lead to the conclusion that the MDCK cells retain regional differentiation of their plasma membranes and the ability to regenerate kidney tubule-like structures in vivo.
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PMID:Retention of differentiated properties in an established dog kidney epithelial cell line (MDCK). 22 73

Both pertussis and cholera toxins inhibit oxytocin-stimulated phosphoinositide turnover in rat myometrium. The actions of pertussis and cholera toxins as well as those of CPTcAMP are reversed by H-8, an inhibitor of protein kinase A. H-8 does not have a major effect on cAMP elevation by the toxins in the presence of oxytocin. The results suggest that the stimulation by oxytocin of phosphoinositide turnover does not involve direct obligatory coupling to a pertussis toxin-sensitive GTP-binding protein. Rather, indirect effects on protein kinase A activation may contribute to the inhibitory effects of both cholera and pertussis toxins. This study suggests that caution must be exercised in interpreting inhibition of phosphoinositide turnover by pertussis toxin in whole cell experiments as indicative of direct involvement of a toxin-sensitive GTP-binding protein.
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PMID:Inhibition of oxytocin-stimulated phosphoinositide turnover in rat myometrium by pertussis and cholera toxins may involve protein kinase A activation. 133 68

Prostaglandin F2 alpha (PGF2 alpha) release from the uterus causes luteolysis in ruminants, and oxytocin is thought to be a regulator of this release. In the present study, we have examined the mechanisms involved in oxytocin stimulation of PGF2 alpha secretion by bovine endometrium in vitro. Endometrial tissue explants, obtained from heifers at Day 19 or 20 (n = 3) and Day 0 (estrus, n = 5) of the estrous cycle, were incubated for 2 h and 6 h, and PGF2 alpha concentration in the medium was determined by radioimmunoassay (RIA). Basal PGF2 alpha release increased for up to 6 h and was significantly stimulated after 2 h of incubation with 100 microU and 1000 microU of oxytocin at Day 0 but not at Day 19 or 20. Secretion of PGF2 alpha was not affected by cholera toxin (10 ng/ml) or the cyclic nucleotide analogs dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate at a concentration of 1 mM. A protein kinase A inhibitor (500 microM) had no effect on the oxytocin-induced release of PGF2 alpha. Both the phorbol ester, 12-myristate-13-acetate (100 mM), and the non-phorbol stimulator of protein kinase C, 1-octanoyl-2-acetylglycerol (500 microM), significantly stimulated PGF2 alpha secretion to the same extent as oxytocin. Neither basal nor stimulated PGF2 alpha release was affected by the calcium ionophore A23187 (0.1-5.0 microM). However, PGF2 alpha secretion was sensitive to cycloheximide (1 microgram/ml) suggesting that protein synthesis may be involved. In conclusion, these data suggest that the stimulation of PGF2 alpha by oxytocin is via the protein kinase C effector pathway.
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PMID:Control of bovine uterine prostaglandin F2 alpha release in vitro. 215 9

The role of inositol phospholipid (IP) hydrolysis in agonist-mediated contractility was examined in rat uterine smooth muscle by comparing carbachol-, oxytocin-, and PGF2 alpha-mediated [3H]IP accumulation and tension generation. In both estrogen- and progesterone-dominated uteri, all three agonists exhibited dose-dependent contractile responses. Agonist potencies (EC50 values) for eliciting [3H]IP accumulation or contractile responses were found to be very similar and did not change significantly between hormonal states. Maximal responses of agonist-mediated [3H]IP accumulation and tension generation were significantly affected by the endocrine state of the uterus and were dependent on the agonist examined. Maximal carbachol- and PGF2 alpha-induced [3H]IP accumulation were found to be elevated in estrogen-dominated relative to progesterone-dominated uteri, whereas maximal forces generated by these two agonists were smaller in progesterone-dominated relative to estrogen-dominated tissues. Oxytocin-induced responses did not differ between hormonal states. To determine whether these differences between [3H]IP accumulation and contractility responses could be attributed to changes in receptor-mediated signal transduction mechanisms, receptor expression and coupling to phospholipase C were studied. Myometrial muscarinic and oxytocin receptors assessed by radioligand binding were found to have three- to four-fold greater capacities in estrogen-dominated than in progesterone-dominated uteri without significant changes in agonist affinities. Agonist-mediated [3H]IP accumulation was potently inhibited by both pertussis and cholera toxins in both hormonal states. These experiments show that estrogen- and progesterone-dominated environments regulate both uterine excitability and contractility and that the mechanisms of this regulation are complex and dependent on the agonist system stimulated.
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PMID:Role of inositol phospholipid hydrolysis in the initiation of agonist-induced contractions of rat uterus: effects of domination by 17 beta-estradiol and progesterone. 283 43

1. In the intact guinea-pig myometrium, carbachol and oxytocin stimulated a specific receptor-mediated phospholipase C activation, catalysing the breakdown of PtdIns(4,5)P2 with the sequential generation of InsP3, InsP2 and InsP. Stimulation of muscarinic receptors also triggered an inhibition of cyclic AMP accumulation caused by prostacyclin. 2. NaF plus AlCl3 mimicked the effects of carbachol and oxytocin by inducing, in a dose-dependent manner, the generation of all three inositol phosphates as well as uterine contractions. AlCl3 enhanced the fluoride effect, supporting the concept that A1F4- was the active species. Under similar conditions, fluoroaluminates activated the guanine nucleotide regulatory protein Gi, reproducing the inhibitory effect of carbachol on cyclic AMP concentrations. 3. Both carbachol- and oxytocin-mediated increases in inositol phosphates, as well as contractions, were insensitive to pertussis toxin, under conditions where the expression of Gi was totally prevented. Cholera toxin, which activates Gs and enhances cyclic AMP accumulation, failed to affect basal or oxytocin-evoked inositol phosphate generation, but induced a slight, though consistent, attenuation of the muscarinic inositol phosphate response, which was similarly evoked by forskolin. 4. The data provide evidence that, in the myometrium, (a) a G protein mediates the generation of inositol phosphates and the Ca2+-dependent contractile event, (b) the relevant G protein that most probably couples muscarinic and oxytocin receptors to phospholipase C is different from Gi and Gs, the proteins that couple receptors to adenylate cyclase, and (c) cyclic AMP does not seem to control the phosphoinositide cycle, but rather exerts a negative regulation at the muscarinic-receptor level.
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PMID:Fluoroaluminates mimic muscarinic- and oxytocin-receptor-mediated generation of inositol phosphates and contraction in the intact guinea-pig myometrium. Role for a pertussis/cholera-toxin-insensitive G protein. 284 25

The mechanism for the luteolytic release of prostaglandin (PG)F2 alpha in swine is not known. This study examined the potential role of oxytocin (OT)-induced phosphoinositide (PI) hydrolysis in promoting PGF2 alpha secretion in vitro from the endometrium of cyclic gilts on Day 15 postestrus. In Experiment 1, endometrial PI hydrolysis was increased (P < 0.05) by 100 nM OT and was increased quadratically (P < 0.05) by LiCl, but was not affected by the LiCl x OT interaction (P > 0.30). PI hydrolysis was maximal at 50 mM LiCl and declined at 100 mM LiCl. In Experiment 2, endometrial PI hydrolysis and PGF2 alpha secretion were similarly increased (P < 0.01) by 0, 0.1, 1, 10, and 100 nM OT in a dose-dependent manner. In Experiment 3, the linear increase in PI hydrolysis occurring 0, 3, 5, 10, and 20 min after treatment was greater (P = 0.01) for tissue treated with 100 nM OT than for the tissue treated with 0 nM OT. The quadratic increase (P < 0.05) in PGF2 alpha secretion occurring 0, 3, 5, 10, and 20 min after treatment was greater (P < 0.05) for tissue treated with 100 nM OT than for the tissue treated with 0 nM OT. In Experiment 4, AlF4- (an activator of Gp and phospholipase C) similarly increased (P < 0.01) PI hydrolysis and PGF2 alpha secretion. In Experiment 5, PI hydrolysis (P < 0.01) and PGF2 alpha secretion (P < 0.05) were increased by 100 nM OT but were not stimulated by cholera toxin (an activator of Gs and adenylate cyclase). Cholera toxin also did not enhance PI hydrolysis and PGF2 alpha secretion in response to 0.1 or 100 nM OT. These results are consistent with the hypothesis that OT may induce PI hydrolysis to stimulate the endometrial secretion of PGF2 alpha during corpus luteum regression in swine.
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PMID:Relationship between phosphoinositide hydrolysis and prostaglandin F2 alpha secretion in vitro from endometrium of cyclic pigs on day 15 postestrus. 762 82

Anterograde transport of cholera toxin subunit B (CTb) was used to study the retinal projections in birds, with an emphasis on retinohypothalamic connections. Pigeons (Columbia livia) were deeply anesthetized and received unilateral intraocular injections of CTb. In addition to known contralateral retinorecipient regions, CTb-immunoreactive fibers and presumptive terminals were found in several ipsilateral regions, such as the nucleus of the basal optic root, ventral lateral geniculate nucleus, intergeniculate leaflet, nucleus lateralis anterior, area pretectalis, and nucleus pretectalis diffusus. In the hypothalamus, CTb-immunoreactive fibers were observed in at least two contralateral cell groups, a medial hypothalamic retinorecipient nucleus, and a lateral hypothalamic retinorecipient nucleus. To compare retinorecipient hypothalamic nuclei in pigeons with the mammalian suprachiasmatic nucleus, double-label experiments were conducted to study the existence of neurophysin-like immunoreactivity in the retinorecipient avian hypothalamus. The results showed that only cell bodies in the medial hypothalamic nucleus contained neurophysin-like immunoreactivity. The results demonstrate CTb to be a sensitive anterograde tracer and provide further anatomical information on the avian equivalent of the mammalian suprachiasmatic nucleus.
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PMID:Cholera toxin mapping of retinal projections in pigeons (Columbia livia), with emphasis on retinohypothalamic connections. 803 20

High concentrations of PGF2 alpha and PGE2 are produced by the uterus during the early postpartum period in cows and may play an important role in both placental separation and uterine involution. In the present study, we have examined the hormonal and intracellular control mechanisms involved in PGF2 alpha and PGE2 secretion by caruncular and allantochorionic tissue in vitro. Tissue explants, obtained about 6 hr postpartum from cows that delivered normally (NFM, n = 10) or cows with retained fetal membranes (RFM, n = 4), were incubated for 6 hr and PGF2 alpha and PGE2 concentrations in the medium were determined by radioimmunoassay. Addition of oxytocin (100 microU/ml), platelet activating factor (PAF, 100 ng/ml) and epidermal growth factor (EGF, 100 ng/ml) had no effect on secretion of PGF2 alpha from the caruncle, but oxytocin and PAF did stimulate PGE2. There was no difference between groups of cows. All three substances stimulated PGF2 alpha from the allantochorion of NFM, but not RFM, cows and stimulated PGE2 secretion from the allantochorion of both groups of cows. Incubation of the tissues with cholera toxin (100 ng/ml), dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cAMP, 1 mM), calcium ionophore A23187 (5 microM) or phorbol ester 12-myristate-13 acetate (PMA, 100 nM) showed that PGF2 alpha secretion is essentially via the calcium-protein kinase C effector pathway. However, calcium-protein kinase C and cAMP second messenger systems appear to be involved in the secretion of PGE2. Prostaglandin secretion was sensitive to cycloheximide in both caruncular and allantochorionic tissues, suggesting that protein synthesis may be involved. In conclusion, these data show that in vitro PGF2 alpha secretion can be modulated by the agonists used only in allantochorion and is essentially via the calcium-protein kinase C effector pathway. PGE2 secretion can be modified in both caruncular and allantochorion tissues and involves both inositol triphosphate-diacylglycerol and cAMP second messenger systems.
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PMID:Control of in vitro prostaglandin F2 alpha and E2 synthesis by caruncular and allantochorionic tissues from cows that calved normally and those with retained fetal membranes. 804 99

The marked up-regulation of oxytocin (OT) receptors in rabbit amnion at term was reproduced in cultured amnion cells by raising intracellular cAMP levels. (Bu)2AMP, forskolin, or cholera toxin caused 2- to 8-fold increases in specific binding of iodinated OT antagonist. The rise in OT receptors involves activation of protein kinase-A activity and protein synthesis, as forskolin's effects were inhibited by H-7 and H-8 and by cycloheximide, respectively. Forskolin treatment also increased specific cross-linking of a photoaffinity derivative of [125I]OT antagonist to a 50-kilodalton electrophoretic band corresponding in size to the amnion OT receptor. Forskolin and (Bu)2cAMP increased OT stimulation of prostaglandin E2 (PGE2) release; PGE2 release elicited by epidermal growth factor or calcium ionophore was unchanged. Forskolin also enhanced stimulation of PGE2 synthesis by phorbol 12-myristate 13-acetate, an activator of protein kinase-C. Because protein kinase-C mediates OT action in amnion cells, forskolin causes increases in both the signal and signal transduction mechanisms. These results suggest that cAMP mediates the exponential-like rise in rabbit amnion OT receptors occurring in vivo at term. The physiological signals increasing cAMP concentrations in amnion may be important for OT stimulation of PGE2 release and, therefore, have a significant role in the initiation and/or progression of labor.
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PMID:Up-regulation of oxytocin receptors in rabbit amnion by adenosine 3',5'-monophosphate. 838 Mar 70

Pulsatile secretion of endometrial prostaglandin (PG)F2 alpha is stimulated by oxytocin (OT) during late diestrus in domestic ruminants (i.e., cattle, sheep and goats) and results in corpus luteum (CL) regression leading to the onset of a new estrous cycle. Pulsatile PGF2 alpha release is also responsible for CL regression in swine, but the stimulus for its secretion from the uterine endometrium is not known. We propose that OT binds to specific OT receptors (OTR) on the endometrium to stimulate phosphoinositide (PI) hydrolysis, thereby activating the inositol trisphosphate (IP3)-diacylglycerol (DAG) second-messenger system to promote pulsatile PGF2 alpha secretion. Exogenous OT administered to cyclic gilts during late diestrus (days 10-16) decreased interestrous interval in three of four experiments. However, OT did not promote CL regression in hysterectomized gilts indicating that the effect of OT was uterine-dependent. Circulating concentrations of 13,14-dihydro-15-keto PGF2 alpha (the major stable metabolite of PGF2 alpha) were increased (p < 0.01) 10 min after i.v. injection of OT on days 14 and 16 in cyclic gilts and on days 10-16 in pregnant gilts, but the magnitude of the response to OT on all days in pregnant gilts was markedly reduced compared to the response in cyclic gilts on days 14 and 16. Mean density and Kd of OTR detected on endometrium of cyclic pigs 15 days post-estrus were 29.2 +/- 5.5 fmol/mg protein and 1.59 +/- 0.23 nM, respectively. Density of OTR was correlated with OT-stimulated PI hydrolysis (r = 0.83, p < 0.05) and PGF2 alpha secretion (r = 0.87, p < 0.10). Endometrial IP3 was increased within 30 seconds after OT treatment and preceded the increase in PGF2 alpha release stimulated by OT. Endometrial PI hydrolysis and PGF2 alpha secretion were similarly increased by AIF4-(phospholipase C activator), but not by cholera toxin (adenylyl cyclase activator). Although OT binding to OTR could be displaced by lysine-vasopressin and lysine-vasopressin stimulated PI hydrolysis, lysine-vasopressin did not stimulate PGF2 alpha release. Distinct receptors for OT and lysine-vasopressin on pig endometrium were confirmed by treatment with 100 nM OT + 100 nM lysine-vasopressin which stimulated PI hydrolysis more than 100-200 nM OT or lysine-vasopressin alone. These results support the hypothesis that OT stimulates phospholipase C to hydrolyze PI, yielding IP3 and DAG second-messengers which promote endometrial PGF2 alpha release during CL regression in pigs.
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PMID:A proposed role for oxytocin in regulation of endometrial prostaglandin F2 alpha secretion during luteolysis in swine. 871 96


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