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

In previous work we reported that oxytocin activates phospholipase-C (PLC) and increases prostaglandin E2 (PGE2) release in amnion. Whether either of the consequences of activation of PLC by oxytocin, activation of protein kinase-C (PKC) or increases in intracellular calcium, directly results in the production of PGE2 is unknown. Phorbol esters (PMA) and epidermal growth factor (EGF) are also known to increase PGE2 release from amnion. In some tissues these agents are capable of activating the PLC postreceptor cascade system. This study was undertaken primarily to explore the mechanism of oxytocin-induced PGE2 production in amnion and secondarily to determine whether common aspects of PGE2 production by oxytocin, PMA, and EGF include activation of PLC or subsequent steps in this cascade followed by new mRNA/protein production. Involvement of PLC was assessed by inositol phosphate (IP1) turnover. IP1 turnover was increased by oxytocin (2.99 +/- 0.31-fold; P less than 0.01), but not by EGF or PMA. PMA inhibited oxytocin-provoked IP1 turnover (P less than 0.05). PKC involvement was initially evaluated with two PKC inhibitors, H7 and staurosporine. Each inhibited PGE2 production by oxytocin as well as that by PMA and EGF in a dose-dependent fashion. With H7, the IC50 for all agents was 5 microM; the IC50 for staurosporine was 2 nM for PMA and oxytocin and 5 nM for EGF. Agonist-induced PGE2 production was also assessed in cells in which PKC activity had been tachyphylaxed with a high concentration of PMA (400 ng/mL for 48 h). In such cells oxytocin and PMA no longer stimulated (P less than 0.001) PGE2 production, but EGF-stimulated PGE2 production was only slightly reduced. PKC involvement is, thus, implicated for oxytocin and PMA. Other enzymes that are inhibited by H7 and staurosporine are implicated in the production of PGE2 caused by EGF. Although tachyphylaxed cells produced no PGE2 with oxytocin, oxytocin increased intracellular calcium to levels higher than those seen in control cells (435 +/- 102 vs. 286 +/- 1.2) Actinomycin-D (P less than 0.001) and cycloheximide (P less than 0.05) inhibited PGE2 production caused by oxytocin, PMA, and EGF. PGE2 production by oxytocin in human amnion cells proceeds by activation of PKC, followed by new protein and mRNA production. Further, in cells without PKC, oxytocin-induced calcium transients do not increase PGE2. The ability of EGF to stimulate PGE2 in cells with no PKC activity also establishes that PKC activation is not a common intracellular step in the induction of PGE2 production by all agents.
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PMID:Protein kinase-C activation is required for oxytocin-induced prostaglandin production in human amnion cells. 202 8

Experiments were conducted to examine the in vitro effects of a phorbol ester and a calcium ionophore on bovine luteal oxytocin (OT) secretion and synthesis and progesterone secretion. Corpora lutea removed from beef heifers on d 8 of an estrous cycle were sliced and incubated for 2 h with .81 nM 12-O-tetradecanoylphorbol-13-acetate (TPA), 1.62 nM TPA or .3 microM calcium ionophore A23187. Both concentrations of TPA increased (P less than .01) OT secretion (ng.g-1.2 h-1; control, 407.1; .81 nM TPA, 494.7; 1.62 nM TPA, 528.1; SE = 21.2). Increased secretion of OT was accompanied by a corresponding increase (P less than .02) in synthesis of the hormone (ng.g-1.2 h-1; control, 368.5; .81 nM TPA, 427.6; 1.62 nM TPA, 492.1; SE = 25.7). Phorbol ester also induced (P less than .025) progesterone secretion (ng.g-1.2 h-1; control, 1,056.2 vs .81 nM TPA, 1,333.3; SE = 86.4). Calcium ionophore increased (P less than .01) OT secretion (ng.g-1.2 h-1; control, 248.9 vs A23187, 327.4; SE = 16) and there was a trend (P = .09) toward increased synthesis of OT in response to the ionophore (control, 124.4 vs A23187, 165.6; SE = 16.4). Because TPA can activate protein kinase C and A23187 increases intracellular calcium, these intracellular constituents probably are involved in promoting secretion of OT and progesterone.
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PMID:Stimulation of bovine luteal oxytocin secretion in vitro by a phorbol ester and calcium ionophore. 211 76

Voltage-dependent Ca2+ channels of the aortic cell line A7r5 were studied using 45Ca2+ flux experiments. Ca2+ channels which have been studied belong to the L-type and are very sensitive to inhibitors and activators in the 1,4-dihydropyridine series as well as to (-)desmethoxyverapamil and d-cis-diltiazem. L-type Ca2+ channels in these smooth muscle cells are not affected by cyclic 8-bromo-AMP and dibutyryl cyclic AMP. However, the activity of these channels is strongly depressed after treatment with diacylglycerols (1-oleyl 2-acetylglycerol and 1,2-dioctanoylglycerol). Phorbol esters, which like diacylglycerols are well-known activators of protein kinase C (the Ca2+- and phospholipid-dependent enzyme), inhibit 70% of Ca2+ channel activity (K0.5 = 25 nM for phorbol 12-myristate 13-acetate and K0.5 = 200 nM for phorbol 12,13-dibutyrate). Phorbol esters that are inactive on kinase C are without effect on Ca2+ channel activity. [Arg8]Vasopressin and bombesin, two peptides that are well known for their action on polyphosphoinositide metabolism, inhibit Ca2+ channel activity to the same extent as active phorbol esters (65-70%). Oxytocin has the same type of effect presumably by acting at the V1-receptor. Both effects of [Arg8]vasopressin and oxytocin are suppressed by [1-(beta-mercapto-beta,beta-diethylpropionic acid)4-valine]arginine vasopressin, a specific vasopressin antagonist at the V1-receptor.
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PMID:Regulation of calcium channels in aortic muscle cells by protein kinase C activators (diacylglycerol and phorbol esters) and by peptides (vasopressin and bombesin) that stimulate phosphoinositide breakdown. 243 72

Addition of the cholinergic agents acetylcholine or carbamylcholine (CCh) to suspensions of human endometrial adenocarcinoma cells (Ishikawa line) preincubated with [3H] myoinositol promoted a rapid concentration-dependent hydrolysis of labeled phosphoinositides to inositol tris-, bis-, and monophosphates with EC50 values (mean +/- SE) of 3.5 +/- 1.6 and 26.5 +/- 4.8 microM, respectively. Atropine inhibition of the CCh effects (Ki = 1.6 +/- 1.3 nM) and the ineffectiveness of nicotinic antagonists indicate involvement of a muscarinic receptor. Both basal and CCh-stimulated production of inositol phosphates were higher in the presence of LiCl. The effect of LiCl on inositol monophosphate accumulation was concentration dependent (1-100 mM). Vasopressin, oxytocin, phenylephrine, histamine, and prostaglandin F2 alpha, had no apparent affect on inositol phosphate levels. Phorbol esters inhibited up to 35% of the effect of CCh on inositol phosphate accumulation. Triphenylethylene antiestrogens at micromolar concentrations increased inositol phosphate accumulation, but inhibited the effects of CCh. However, the rapid uptake of trypan blue observed after exposure to 10 microM tamoxifen suggests an alteration of the plasma membrane which may affect signal-transducing systems. The effects of CCh on the production of inositol phosphates and the expected concomitant liberation of diacylglycerol by transformed epithelial cells of human endometrium are of potential significance in normal endometrial physiology, since cholinergic innervation of endometrial glands has been reported, and the role of hormonally stimulated phosphoinositide hydrolysis in secretory mechanisms has been demonstrated in many systems.
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PMID:Regulation of phosphoinositide hydrolysis in transformed human endometrial cells. 284 Feb 72

One of the roles previously reported for protein kinase C (PKC) is modulation of the activity of the phosphatidylinositol signaling pathway. Studies were performed to test the hypothesis that activation of PKC results in inhibition of agonist-stimulated phasic myometrial contractions: contractions that appear to be mediated by phosphatidylinositol signaling mechanisms comparable to those producing cytosolic calcium oscillations. In vitro isometric contraction studies were performed using myometrium from adult Sprague-Dawley rats. Oxytocin and aluminium fluoride (a G-protein activator) produced comparable increases in phasic contractile activity. Phorbol 12,13-dibutyrate (PDB) significantly suppressed agonist-stimulated phasic myometrial contractions; in contrast, phorbol 13,20-diacetate (PDA), an inactive phorbol ester, had no significant effect on myometrial contractions. Prolonged exposure of myometrial tissue to PDB failed to down-regulate myometrial PKC and had no consistent effect on spontaneous and oxytocin-stimulated phasic contractions. These studies have provided support for a role for PKC as an intracellular regulator of the phosphatidylinositol signaling pathway, which itself appears to be part of the myometrial calcium oscillator that results in agonist-stimulated phasic myometrial contractions.
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PMID:Protein kinase C, an inhibitor of oxytocin-stimulated phasic myometrial contractions. 819 66