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

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

The effect of protein kinase C activation and dibutyryl cyclic AMP on oxytocin secretion by ovine luteal tissue slices was investigated. Several putative regulators of luteal oxytocin secretion were also examined. Oxytocin was secreted by luteal tissue slices at a basal rate of 234.4 +/- 32.8 pmol/g per h (n = 24) during 60-min incubations. Activators of protein kinase C: phorbol 12, 13-dibutyrate (n = 8), phorbol 12-myristate, 13-acetate (n = 4) and 1,2-didecanoylglycerol (n = 5), caused a dose-dependent stimulation of oxytocin secretion in the presence of a calcium ionophore (A23187; 0.2 mumol/l). Phospholipase C (PLC; 50-250 units/l) also caused a dose-dependent stimulation of oxytocin secretion by luteal slices. Phospholipase C-stimulated oxytocin secretion was potentiated by the addition of an inhibitor of diacylglycerol kinase (R59 022; n = 4). These data suggest that the activation of protein kinase C has a role in the stimulation of luteal oxytocin secretion. The results are also consistent with the involvement of protein kinase C in PLC-stimulated oxytocin secretion. The cyclic AMP second messenger system does not appear to be involved in the control of oxytocin secretion by the corpus luteum.
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PMID:Regulation of oxytocin secretion by the ovine corpus luteum: effect of activators of protein kinase C. 215 85

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

Release of oxytocin by sliced or minced sheep luteal tissue in vitro was stimulated up to 1.6- and 2.3-fold by arachidonic acid and the calcium ionophore A23187 respectively. Prostaglandin (PG) F2 alpha and the PGF2 alpha analogue cloprostenol, and other potential agonists known to be active in vivo, including noradrenaline and acetylcholine, were ineffective, as was the phorbol ester tetradecanoylphorbol acetate (TPA). The ineffectiveness of PGF2 alpha was not due to a general unresponsiveness of the tissue in vitro, as PGF2 alpha reduced LH stimulation of tissue concentrations of cyclic AMP and activated inositol lipid hydrolysis. The effect of arachidonic acid was accompanied by release from the tissue of the cytosolic enzyme lactate dehydrogenase (at arachidonic acid concentrations below those required to release oxytocin) and its effect on oxytocin and lactate dehydrogenase release was mimicked by oleic and linolenic acids; arachidonic acid was concluded to act by a non-physiological physicochemical effect without conversion to an eicosanoid. As PGF2 alpha in vitro is known to raise intracellular Ca2+ concentrations in the large luteal cells that secrete oxytocin, and as A23187 stimulates oxytocin release in vitro in the presence and absence of TPA, it is concluded that in-vitro incubation results in an artifactual blockade of the oxytocin-releasing action of PGF2 alpha at an unidentified point distal to the effect on intracellular Ca2+.
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PMID:Effects of prostaglandin F2 alpha and other potential secretagogues on oxytocin secretion and second messenger metabolism in the ovine corpus luteum in vitro. 216 27

A bland procedure, conducted in ice, is described for the extraction with HCl of smooth-muscle-contracting substances from plexus-containing ileal longitudinal muscle (l.m.) sheets obtained mainly from rabbits and some guinea-pigs. The spasmogenic activity in rabbit extracts was distinguished from acetylcholine, histamine and 5-hydroxytryptamine by antagonists; and from prostaglandins, by its insolubility in ether at acid pH and by pretreatment of the animals with indomethacin. The fact that it contracts the separated l.m. of the guinea-pig ileum, whether plexus-containing or plexus-free, and in atropine distinguishes it also from methionine-enkephalin, somatostatin, 13-norleucine motilin, bombesin, and cholecystokinin octapeptide (CCK8). This activity was partially purified, first by several partitions with ether at pH 1.4-2.2 and then by treatment at pH 4.5-5 with lead acetate. The virtual absence of ATP was confirmed by the firefly bioluminescence technique. The guinea-pig-ileum-contracting component in the partially purified extracts was destroyed by pepsin, chymotrypsin and DPCC-treated trypsin, indicating its peptide nature and distinguishing it from oxytocin, vasopressin, bradykinin, etc. In parallel assays the partially purified rabbit extracts were considerably more active than Substance P on jird or rat ascending colons than on the guinea-pig l.m., suggesting the presence of a second spasmogenic component in the extracts. In guinea-pig extracts the partially purified activity was 8-16 times greater when plexus-containing than when plexus-free, pointing to Auerbach's plexus as the source of the activity.
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PMID:Extraction and partial purification of spasmogenic substances in Auerbach's plexus. 242 21

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

1. Isolated nerve endings from rat neurohypophyses were permeabilized with digitonin in order to gain access to the cytoplasm. Release of vasopressin (AVP), oxytocin and the neurophysins was studied under different experimental conditions. 2. Hormone release, which occurred by exocytosis, was Ca2+ dependent. Half-maximal release was observed at ca. 1.7 microM-Ca2+ in contrast to ca. 300 microM for K+-induced hormone secretion from non-permeabilized neurosecretosomes. 3. Release also occurred when the neurosecretosomes were challenged with Ca2+ 20 min after digitonin treatment. This suggests that the isolated nerve endings remain permeable after treatment with digitonin. 4. Although hormone release was potentiated in the presence of ATP, and to a lesser extent with guanosine triphosphate (GTP), secretion occurred in the absence of nucleotides. 5. Replacement of K+ as the major cation by Na+ did not modify the secretory response to a Ca2+ challenge. Release, although reduced, still occurred when KCl was replaced by sucrose. 6. Compared to glutamate, Cl-, Br- and I- did not modify the Ca2+-independent release. This release was increased in the presence of SCN-. The order of effectiveness of the anions studied in inhibiting the Ca2+-dependent release was glutamate less than Br- = Cl- = I- less than SCN-. 7. Increasing the osmolarity of the perfusate inhibited the Ca2+-dependent release of AVP and oxytocin. 8. Vincristine, which binds to microtubules, had no effect on the secretory process. 9. Ca2+ dependent AVP release was partially inhibited by the calmodulin antagonist trifluoroperazine. 10. Hormone release was potentiated by the protein kinase C activator, 4-beta-phorbol 12-myristate acetate (TPA). 11. Whereas 0.2 microM-Ca2+ induced a barely significant increase in AVP release, inositol 1,4,5-triphosphate, in the continued presence of 0.2 microM-Ca2+, produced a large secretory response. 12. 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS), an inhibitor of Cl- permeability, reduced the Ca2+-dependent AVP release. 13. Carbonyl cyanide m-chlorophenylhydrazone (CCCP), which reduces the transmembrane potential of isolated neurohypophysial granules, inhibited the Ca2+-dependent hormone secretion. 14. Maximal hormone release occurred at pH 6.6. 15. It is concluded that the permeabilized neurosecretosomes represent an excellent model for studying the minimal requirements for neurosecretion.
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PMID:Requirements for hormone release from permeabilized nerve endings isolated from the rat neurohypophysis. 245 Oct

Some studies have indicated that insulin was able to increase the level of free cytosolic calcium in adipocytes [e.g. 7]. The present study was designed to examine this phenomenon. Insulin did not increase free cytosolic calcium, however oxytocin, vasopressin, alpha-adrenergic agonists and ATP did increase free cytosolic calcium in adipocytes. Other agonists which also did not alter calcium were epidermal growth factor, angiotensin II, glucagon, and beta-adrenergic agonists. The effect of oxytocin at increasing free cytosolic calcium was inhibited by activation of protein kinase C with phorbol 12-myristate 13-acetate and by ADP ribosylation of a Gi like protein with islet activating protein. The hormones that did increase cytosolic free calcium did so by mobilizing internal calcium and by promoting calcium influx. Even though insulin did not increase free cytosolic calcium, it was able to attenuate the alpha-adrenergic mediated increase in cytosolic free calcium. The fact that certain hormones can increase the level of the second messenger calcium in adipocytes implies that it may be a key intracellular regulator of adipocyte function as it is in many other tissues.
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PMID:Effect of hormones on cytosolic free calcium in adipocytes. 251 19

It has been suggested that during the oxytocin-induced hydrosmotic response, water crosses the luminal membrane of urinary bladder epithelium cells through membrane-spanning proteins. Although specific inhibitors of osmotic water transport have not been found, certain sulfhydryl reagents such as mercurial compounds may help to identify the proteins involved in this permeation process. We tested the effects of p-chloromercuribenzene sulfonate (PCMBS) and of fluorescein-mercuric acetate (FMA) on the net water flux, the microtubule and microfilament structures of the frog urinary bladder, and the distribution of intramembrane particle aggregates in the luminal membrane. We observed that: (i) 5 mM PCMBS at pH 5 and 0.5 mM FMA at pH 8 added to the mucosal bath at the maximum of the response to oxytocin partially inhibited the net water flux. Inhibition then increased progressively when the preparation was repeatedly or continuously stimulated, until it reached a maximal inhibition at 120 min. This inhibition was not reversed even when cystein was added in the mucosal bath. PCMBS and FMA effects were also observed when cyclic AMP (3',5' cyclic adenosine monophosphate) was used to increase water permeability, (ii) PCMBS mucosal pretreatment did not modify the basal water flux but potentiated the inhibitory effect of PCMBS or FMA on the hydrosmotic response to oxytocin. (iii) Microtubule and microfilament network, visualized in target cells by immunofluorescence, was not affected by PCMBS. (iv) The maximal PCMBS or FMA inhibition was not associated with a reduction of aggregate surface area in the apical membrane. The persistence of the intramembrane particle aggregates associated with the oxytocin-induced hydrosmotic response during the net water flux inhibition by PCMBS, suggests that the PCMBS effect occurs possibly at the level of sulfhydryl groups of the water channel itself.
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PMID:Effect of mercurial compounds on net water transport and intramembrane particle aggregates in ADH-treated frog urinary bladder. 255 73

The excitatory neurotransmitter, L-glutamate (0.5 M, pH 7.4), or the organic acid, acetate (0.5 M, pH 7.4), was microinjected (50 nl over 2 min) directly into the paraventricular nuclei (PVN) of pentobarbital sodium-anesthetized rats while arterial blood pressure and heart rate and plasma adrenocorticotropic hormone (ACTH), vasopressin, and oxytocin were measured. Activation of PVN neurons with L-glutamate led to increases in plasma ACTH, vasopressin, and oxytocin and a profound bradycardia (approximately 80 beats/min) with little change in arterial blood pressure. Microinjection of acetate had no effect on the above variables. The decrease in heart rate was shown to be dependent on the concentration of glutamate injected and the volume of injectate. The bradycardia was mediated through the autonomic nervous system because ganglionic blockade (pentolinium tartrate) eliminated the response; atropine and propranolol severely attenuated the bradycardia. The bradycardia was greatest when L-glutamate was microinjected into the caudal PVN. Injections into the rostral PVN or into nuclei surrounding the PVN led to small or nonsignificant decreases in heart rate. Focal electric stimulation (2-50 microA) of the PVN also led to decreases in heart rate and arterial blood pressure. These data suggest that activation of PVN neurons leads to the release of ACTH, vasopressin, and oxytocin from the pituitary and a bradycardia that is mediated by the autonomic nervous system.
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PMID:Paraventricular stimulation with glutamate elicits bradycardia and pituitary responses. 256 5


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