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)

Vasopressin and oxytocin both stimulated inositol phosphate accumulation in isolated uterine decidua cells. Pretreatment of cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) prevented this agonist-induced phosphoinositide hydrolysis. TPA (0.1 microM) alone had no effect on basal inositol phosphate accumulation, but stimulated phosphoinositide deacylation, as indicated by a 2-fold increase in lysophosphatidylinositol and glycerophosphoinositol. TPA also stimulated a dose-related release of arachidonic acid from decidua-cell phospholipid [phosphatidylcholine (PC) much greater than phosphatidylinositol (PI) greater than phosphatidylethanolamine]. The phorbol ester 4 beta-phorbol 12,13-diacetate (PDA) at 0.1 microM had no effect on arachidonic acid mobilization. The TPA-stimulated increase in arachidonic acid release was apparent by 2 1/2 min (116% of control), maximal after 20 min (283% of control), and remained around this value (306% of control) after 120 min incubation. TPA also stimulated significant increases in 1,2-diacylglycerol and monoacylglycerol production at 20 and 120 min. Although the temporal increases in arachidonic acid and monoacylglycerol accumulation in the presence of TPA continued up to 120 min, that of 1,2-diacylglycerol declined after 20 min. In decidua cells prelabelled with [3H]choline, TPA also stimulated a significant decrease in radiolabelled PC after 20 min, which was accompanied by an increased release of water-soluble metabolites into the medium. Most of the radioactivity in the extracellular pool was associated with choline, whereas the main cellular water-soluble metabolite was phosphorylcholine. TPA stimulated extracellular choline accumulation to 183% and 351% of basal release after 5 and 20 min respectively and cellular phosphorylcholine production to 136% of basal values after 20 min. These results are consistent with a model in which protein kinase C activation by TPA leads to arachidonic acid mobilization from decidua-cell phospholipid by a mechanism involving phospholipase A-mediated PI hydrolysis and phospholipase C-mediated PC hydrolysis, coupled with further hydrolysis of the 1,2-diacylglycerol product.
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PMID:Stimulation of phospholipid hydrolysis and arachidonic acid mobilization in human uterine decidua cells by phorbol ester. 282 48

In myometrium from pregnant rats, 100 nM-TPA elevated resting tension and initially slightly enhanced the contraction induced by 138 mM-KCl. After 20 min this force development significantly declined. In saponin-treated skinned myometrial cells from pregnant rats, 100 nM-TPA enhanced the contraction induced by 0.3 microM-Ca2+, but reduced that induced by 1 microM-Ca2+. These findings suggest that the excitatory and inhibitory actions of TPA on the myometrium are probably due to its action on the contractile proteins. In myometrium from non-pregnant rats, TPA affected neither the resting tension, nor the amplitude of the evoked contractions, nor the Ca2+-induced contractions in skinned myometrium. While TPA only affected tension development in pregnant rats, both 1 mM-carbachol and 90 nM-oxytocin induced a tonic contraction in Ca-free solution independently of the hormonal status of the rats. The latter finding makes it unlikely that activation of protein kinase C is involved in the agonist-induced tonic force development in Ca-free solution.
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PMID:TPA- and agonist-induced force development in myometrium from pregnant and non-pregnant rats. 291 51

Five new concepts concerning the control of corpus luteum function in the cow have been developed in recent years. Prostacyclin (PGI-2) plays a luteotrophic role. Conversely, products of the lipoxygenase pathway of arachidonic acid metabolism, particularly 5 hydroxyeicosatetraenoic acid (5-HETE), play luteolytic roles. Luteal cells arise from two sources. The small luteal cells are all of theca cell origin; the large cells found early in the cycle (Days 2-6) are mainly of granulosa cell origin. However, a population of large cells found after Day 10 of the cycle are of theca cell origin. Oxytocin of luteal cell origin plays a role in development of the corpus luteum and possibly in its regression. The recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system, as well as the LH-cAMP system, is involved in control of progesterone synthesis in the bovine corpus luteum. Progesterone synthesis in the small theca-derived luteal cells is primarily controlled by the cAMP system. However, elevated intracellular calcium diminishes cAMP-mediated progesterone synthesis in these cells. These findings modify our current concepts of the mechanisms of control of progesterone secretion by the corpus luteum and suggest several new lines of research.
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PMID:Hammond memorial lecture. New concepts of the control of corpus luteum function. 302 24

Our laboratory has reported previously the characteristics of specific AVP binding to rat hippocampal synaptic membranes (SPM) in the presence of Ni2+ [Costantini MG, Pearlmutter AF: J Biol Chem 259: 11739-11745, 1984]. We extended our investigation to determine the effects of Ni2+, (AVP), and AVP analogs on SPM protein phosphorylation. Ni2+ (5 mM) caused a dramatic reduction in phosphorylation of most SPM phosphoproteins. The most prominent protein which is phosphorylated in SPM has a molecular weight of 48 kilodaltons (KDa) and has been named B50 or F1; this protein shows altered phosphorylation in vitro in response to long-term potentiation in vivo as well as changes induced by exposure of SPM to ACTH (1-24), dopamine, and somatostatin. AVP and related peptides reduced phosphorylation of this pre-synaptic phosphoprotein in the following order of potency: AVP = oxytocin greater than DG-AVP greater than dDAVP greater than d(CH2)5Tyr(Me)AVP = [pGlu4,Cyt6]AVP-(4-9). Except for the pressor antagonist d(CH2)5Tyr(Me)AVP, this corresponds to their relative efficacy in displacing 3H-AVP from high-affinity specific binding sites on rat hippocampal synaptic membranes. Ni2+ did not alter the degree of inhibition caused by the peptides. When SPM were treated with AVP after the attainment of maximum 32P incorporation, AVP inhibited dephosphorylation over a 30-min period. Our results show that AVP can alter both phosphorylation and dephosphorylation of hippocampal SPM phosphoproteins in vitro; the direction of these effects depends upon experimental conditions. Since B50/F1 is known to be a substrate for protein kinase C, AVP may act by inhibition of protein kinase C activity, either directly or indirectly.
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PMID:Effects of arginine vasopressin on protein phosphorylation in rat hippocampal synaptic membranes. 303 58

Corpora lutea from sheep and cows as well as human and primates contain both large and small steroidogenic cells exhibiting distinct functional properties. Only the small cells seem to be able to respond in vitro to LH stimulation by raising their progesterone secretion. However, the entire progesterone secretion of the corpus luteum has been shown to be regulated in vivo by LH in the primate. The LH steroidogenic action involves the activation of membrane adenylate cyclase whose molecular mechanism has been elucidated. Then a rise in intracellular cyclic AMP induces phosphorylation by a cyclic AMP dependent protein kinase of steroidogenic protein targets which have not yet been completely identified. In sheep and cows, luteolysis is believed to be the consequence of a series of reciprocal interactions between the corpus luteum whose large cells secrete pulses of oxytocin in response to PGF2 alpha luteolysin and the endometrium which secretes pulses of PGF2 alpha in response to oxytocin. The secretion of endometrial PGF2 alpha can only begin after the induction of endometrial receptors by estradiol, from the preovulatory follicles. Similarly in women and primates luteolysis, which does not require the presence of the uterus, could be the consequence of local reciprocal paracrine interactions between luteal cells of different types. These interactions are likely to involve PGF2 alpha' oxytocin and estradiol. The biochemical mechanism responsible for the inhibition by PGF alpha of LH induced progesterone secretion in luteal cells could involve a stimulation in the cell membrane of protein kinase C and the rise of cytosolic Ca+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Recent concepts concerning the corpus luteum]. 307 52

Two activators of protein kinase C, phorbol 12,13-dibutyrate (PDBu) and 1-oleoyl-2-acetylglycerol (OAG), augment electrically stimulated vasopressin and oxytocin secretion from the nerve terminals of the isolated rat neurointermediate lobe. The increased hormone release produced by PDBu is specific to the beta-phorbol conformation, and is dependent upon electrical stimulation in the presence of calcium. Furthermore, the potentiation of release was evident during low frequency stimulation (4 Hz) but not when the same number of pulses were applied at 20 Hz. This occlusion of the phorbol ester's effect by high-frequency stimulation suggests that activation of protein kinase C may play a role in the normal process of frequency-dependent facilitation of secretion in the neurohypophysial system.
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PMID:Activators of protein kinase C potentiate electrically stimulated hormone secretion from the rat's isolated neurohypophysis. 316 64

Evidence was cited to show that: (1) prostacyclin (PGI2) plays a luteotrophic role in the bovine corpus luteum and that products of the lipoxygenase pathway of arachidonic acid metabolism, especially 5-hydroxyeicosatetraenoic acid play luteolytic roles; (2) oxytocin of luteal cell origin plays a role in development, and possibly in regression, of the bovine corpus luteum; and (3) luteal cells arise from two sources; the characteristic small luteal cells at all stages of the oestrous cycle and pregnancy are of theca cell origin; the large cells are of granulosa cell origin early in the cycle, but a population of theca-derived large cells appears later in the cycle. Results of in vitro studies with total dispersed cells and essentially pure preparations of large and small luteal cells indicate that: (1) the recently described Ca2+-polyphosphoinositol-protein kinase C second messenger system is involved in progesterone synthesis in the bovine corpus luteum; (2) activation of protein kinase C is stimulatory to progesterone synthesis in the small luteal cells; (3) activation of protein kinase C has no effect on progesterone synthesis in the large luteal cells; and (4) protein kinase C exerts its luteotrophic effect in total cell preparations, in part at least, by stimulating the production of prostacyclin. The protein kinase C system may cause down regulation of LH receptors in the large cells.
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PMID:Control of steroidogenesis in small and large bovine luteal cells. 332 92

The BE(2)-M17 and BE(2)-C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin-releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin-1 alpha, as well as various neurotransmitters and peptides. Nanomolar concentrations of the phorbol ester--phorbol 12 myristate 13--acetate (TPA), increased intracellular CRF content in both cell lines while increasing secretion only in the BE(2)-M17 cell. Nanomolar concentrations of dexamethasone were not able to alter basal levels of secretion and content in either cell type. However, in the BE(2)-M17 cell but not the BE(2)-C cell, the same concentrations of dexamethasone added to 30 microM forskolin augmented levels of CRF secretion and content. Likewise, the same augmented response in CRF secretion and content was seen only in the BE(2)-M17 cell line when nanomolar concentrations of dexamethasone were added to 20 nM TPA. Furthermore, only in the BE(2)-M17 cell line were micromolar levels of the biogenic amine serotonin able to increase levels of CRF secretion and content. No effects on CRF in both cell lines were demonstrable with picomolar levels of interleukin-1 alpha as well as micromolar levels of acetylcholine, norepinephrine, arginine-vasopressin, oxytocin, and angiotensin-II. The potential usefulness of these cells as models of central nervous system or placental CRF-containing neurons is discussed.
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PMID:Regulation of corticotropin-releasing factor secretion and synthesis in the human neuroblastoma clones- BE(2)-M17 and BE(2)-C. 755 Feb 93

These studies sought to test the hypothesis that potassium-stimulated phasic myometrial contractions utilize cytosolic calcium oscillation-like mechanisms comparable to those activated in response to oxytocin. Uterine tissue was obtained from pro-oestrus/oestrus Sprague-Dawley rats. In vitro isometric contraction studies were performed using longitudinal myometrial strips; computer digitalized contraction data were analyzed for contraction area, and normalized for tissue cross-section area. Dose-response studies were performed using potassium chloride with and without inhibitors of cytosolic calcium oscillation mechanisms. Qualitative inositol-phosphate production studies were performed after preloading uterine tissue with [3H]inositol; subsequently, the individual inositol-phosphates produced in response to stimulation were isolated by anion exchange chromatography. Potassium chloride over a concentration of 10 to 30 mM produced a dose-related increase in phasic contractile activity. The potassium-stimulated phasic contractions were significantly suppressed in response to inhibition of phospholipase C, stimulation of protein kinase C, inhibition of calcium-induced calcium release, and prevention of extracellular calcium influx. The qualitative inositol-phosphate production studies confirmed activation of phospholipase C in response to 20 mM potassium. These studies have provided support for the hypothesis that potassium-stimulated phasic myometrial contractions activate intracellular signal transduction mechanisms comparable to those activated in response to hormonal uterotonic agonists.
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PMID:Potassium chloride effects on the hormonal signal transduction mechanisms underlying phasic myometrial contractions. 759 44

The regulation of prostaglandin E2 and prostaglandin F2 alpha in primary cultures of epithelial and stromal cells of bovine endometrium was investigated using two physiological agents, oxytocin and platelet-activating factor, and the protein kinase C activator, 4 beta-phorbol 12-myristate 13-acetate. At the basal level, epithelial cells produced more prostaglandin F2 alpha than did stromal cells (P < or = 0.0001) and stromal cells produced more prostaglandin E2 than did epithelial cells (P < or = 0.0001). In the presence of oxytocin, production of prostaglandin E2 and F2 alpha increased in a dose-dependent manner, only in epithelial cells. Stromal cells did not respond to oxytocin, suggesting that the oxytocin response is cell type specific, acting preferentially on the cell type in which prostaglandin F2 alpha is the major prostaglandin produced. Platelet-activating factor increased prostaglandin E2 and prostaglandin F2 alpha production in epithelial cells at 1 and 10 pmol l-1 (PGE2: 10 pmol l-1, P < or = 0.01; PGF2 alpha: 1 pmol l-1, P < or = 0.02). Stromal cells also responded to platelet-activating factor, but only at high concentrations (PGE2: 0.1 mumol l-1, P < or = 0.001; PGF2 alpha: 0.1 mumol l-1, P < or = 0.0001). These results further demonstrate the differences in epithelial and stromal cells; epithelial cells are more sensitive to platelet-activating factor than are stromal cells. Phorbol 12-myristate 13-acetate increased prostaglandin production in a dose-dependent manner in both epithelial and stromal cells, indicating that protein kinase C activation can increase prostaglandin production in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cell type specificity and protein kinase C dependency on the stimulation of prostaglandin E2 and prostaglandin F2 alpha production by oxytocin and platelet-activating factor in bovine endometrial cells. 761 96


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