Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of TPA (12-O-tetradecanoyl phorbol-13-acetate), a potent tumor promoter, on immunoreactive somatostatin release was investigated using the isolated perfused rat stomach. TPA at the concentration as low as 20nM significantly stimulated the somatostatin release from isolated perfused rat stomach. The integrated net output of somatostatin induced by TPA was dose-dependent in a range of 5 - 50nM TPA. Since TPA is known to activate C-kinase specifically at a low dose (less than 20nM), these findings suggest that C-kinase system may be involved in the regulation of somatostatin release in rat stomach.
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PMID:12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates somatostatin release from isolated perfused rat stomach. 286 48

We and others have suggested previously that the binding of somatostatin to its receptors in the pancreas is regulated by not only somatostatin analogs but also cholecystokinin analogs in proportion to their known biological potencies. To clarify the precise mechanism by which unrelated peptides modulate somatostatin binding, the effect of a phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), or a synthetic diacylglycerol analog, 1-oleyl-2-acetylglycerol (OAG), on [125I-Tyr1]somatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37 degrees C with 100 ng/ml TPA maximally reduced subsequent labeled somatostatin binding to acinar membranes. The inhibitory effect of TPA on the somatostatin binding was dependent on the dose used or the time and temperature of pretreatment. These effects of TPA were almost mimicked by the treatment of acini with OAG. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by TPA or OAG pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. A specifically labeled single band of Mr = 90,000 obtained with a photoaffinity cross-linking study indicates that the somatostatin-binding sites are the same somatostatin receptor as previously described. Moreover, the intensity of the Mr = 90,000 band was dramatically decreased when acini were treated with increasing concentrations of TPA, a finding consistent with TPA-induced decrease in binding capacity. Such an inhibitory effect of TPA was abolished when pretreatment of acini with TPA was performed in the presence of Ca2+-chelating compounds such as EDTA and EGTA or phospholipid-interacting drugs such as chlorpromazine and tetracaine. Interestingly, the combined treatment of TPA and Ca2+ ionophore A23187 caused synergistic inhibition of the subsequent labeled somatostatin binding to acinar membranes, although Ca2+ ionophore itself almost failed to affect the somatostatin binding. These results suggest, therefore, that TPA or OAG can modulate somatostatin binding to its receptors on rat pancreatic acinar cell membranes, presumably through activation of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C); and the activated protein kinase C and intracellular Ca2+ mobilization presumably act to modulate the pancreatic acinar somatostatin receptors synergistically.
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PMID:Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes. 286

The present study was undertaken to examine the effects of 12-0-tetradecanoyl-phorbol-13-acetate (TPA), one of the potent tumor promoting agents, on GH, TSH and PRL release by rat adenohypophyseal dispersed cells and fragments, using a superfusion technique. TPA (10(-6) to 10(-5) M) stimulated GH release from acutely dispersed rat adenohypophyseal cells. Neither TSH nor PRL was affected, but both were increased by TRH in a dose-dependent fashion (10(-9) to 10(-7) M). In fragments, TPA (10(-8) to 10(-6) M) elicited a dose-related release of GH. Exposure of the fragments to 10(-6) M TPA for 5 min promptly caused a 5-fold increase in GH release which continued for at least 40 min after stopping the stimulation. The addition of somatostatin (SRIF) (10(-7) M) decreased basal GH release and abolished GH release induced by 10(-6) M TPA. In contrast to GH, neither TSH nor PRL release was affected by TPA, but both were stimulated by TRH. These results indicate 1) that GH release is more sensitive to stimulation with TPA in normal rat anterior pituitaries in vitro than the release of TSH and PRL, and 2) that SRIF abolishes TPA-induced GH release.
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PMID:Effects of phorbol ester on GH, TSH and PRL release by superfused rat adenohypophysis. 286 85

The authors noticed effects of somatostatin on muscarinic acetylcholine receptors (mAchR) in the rat hippocampus from binding experiments. Saturation experiments of 3H-oxotremorine-M-acetate (3H-oxo-M) buffered with Krebs-Henseleit solution revealed that there were two binding sites with very high and low affinities whose Kd values were 1.2 nM and 445.8 nM, respectively. Adding somatostatin in this incubation medium caused an increase in the Kd value of the high affinity binding site with no change in the Bmax value. As for the low affinity binding site, Kd and Bmax values were too large to determine the effect of somatostatin. The oxotremorine/3H-N-methyl-scopolamine competition experiments indicated the presence of two components of agonist binding sites. The inhibition curve after adding somatostatin fitted best to a single homogeneous binding site whose Ki value was consistent with the dissociation constant of the oxotremorine low affinity binding site. Therefore, it seems that somatostatin accelerates conformational changes of the oxotremorine high affinity binding site to the low affinity binding state. A single binding site with a Kd value of 30.9 nM was obtained by switching the buffer to Na-K phosphate solution. The affinity of this binding site was likewise inhibited by somatostatin. The inhibitory effect of somatostatin-28 was more marked than that of [D-trp8] somatostatin. The above-mentioned effects of somatostatin was limited to mAchR agonist binding.
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PMID:Effects of somatostatin on muscarinic acetylcholine receptor binding in the rat hippocampus. 287 Dec 10

Recent studies suggest that 12-O-tetradecanoylphorbol 13-acetate (TPA), one of a family of phorbol esters that are known tumor promoters, can activate intracellular Ca2+, phospholipid-dependent protein kinase (protein kinase C) directly. To examine the possible involvement of protein kinase C-mediated mechanisms in regulating gastric somatostatin release, we studied the effects of TPA on isolated enriched canine gastric somatostatin cells in short-term culture. TPA markedly stimulated somatostatin release such that nearly 10% of total cellular content of somatostatin was released into media within 2 h of incubation. Among the phorbol compounds tested, TPA was the most potent, with half-maximum effective dose (ED50) obtained at a dose of 5 X 10(-9) M. Phorbol 12,13-dibutyrate (PDBu) also stimulated somatostatin release but with only 5% of the potency of TPA, whereas phorbol compounds with no biological activity in other systems failed to stimulate somatostatin release. In the absence of extracellular Ca2+, the effects of TPA were significantly attenuated. In contrast, stimulation of somatostatin release by forskolin (10(-4) M) was not affected by Ca2+ deprivation but was potentiated by TPA. No such potentiation was observed when TPA was combined with the Ca2+ ionophore A23187. Carbamylcholine (10(-5) M), which inhibits the stimulatory actions of beta-adrenergic agonists or dibutyryl cyclic adenosine monophosphate on somatostatin cells, also inhibited TPA-induced somatostatin release. These data suggest the presence of dual stimulatory mechanisms for gut somatostatin release, both of which are susceptible to inhibition by muscarinic agonists.
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PMID:Phorbol esters stimulate somatostatin release from cultured cells. 287 64

The effect of somatostatin on cyclic AMP-protein kinase system and lipid metabolism was studied in mouse brain. Subcutaneous injection of the peptide decreased the cyclic AMP and cyclic GMP levels (70% and 60% respectively) as well as protein kinase and triglyceride lipase activities (30%). Cyclic AMP binding protein activity was not affected. Experiments carried out with [14C]acetate as precursor of lipids seem to indicate that somatostatin blocks the fatty acid turnover. On the other hand, the general decrease of 32P incorporation into all phospholipids by somatostatin suggests that the peptide interferes with the precursor uptake into phospholipids. The findings reported here indicate that somatostatin has a role on brain metabolism and further add more data in support for its neuromodulating action.
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PMID:Somatostatin effects on the cyclic AMP system and lipid metabolism in mouse brain. 287 18

The effect of somatostatin on muscarinic receptors (mAchR) was investigated through saturation experiments of [3H]oxotremorine-M-acetate and oxotremorine/[3H]N-methyl-scopolamine competition experiments. Somatostatin converted oxotremorine high affinity binding sites to low affinity sites in the hippocampus and cerebral cortex whose mAchR were dominantly of M1 type. Somatostatin did not alter agonist binding in the medulla-pons where M2 receptors were abundant. Therefore, the effect of somatostatin on mAchR seems to be selective to high affinity binding sites of M1 receptors.
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PMID:Is the effect of somatostatin on muscarinic receptors selective to M1 type? 287 70

The brain peptide human growth hormone releasing factor (1-40) (GRF), which stimulates adenylate cyclase activity in the anterior pituitary, is the predominant hormone signal for pituitary growth hormone (GH) release. Activators of protein kinase C such as teleocidin and 4 beta-phorbol 12-myristate 13-acetate (PMA) double the cyclic AMP accumulation induced by GRF, with no apparent effect on GRF potency; an inactive 4-alpha-PMA has no such action in cultured anterior pituitary cells. This PMA potentiation can be measured as early as 60 s, is maximal by 15 min, and wanes such that by 3-4 h there is no such amplifying effect of PMA. PMA, phorbol 12,13-dibutyrate, and teleocidin ED50 values for potentiating GRF activity are similar to those obtained for direct protein kinase C activation. The major inhibitory peptide somatostatin reduced both GRF- and GRF + PMA-stimulated cyclic AMP accumulation. Pertussis toxin totally blocked this somatostatin action without affecting the degree of maximal GRF potentiation achieved with PMA. Thus, the pertussis toxin target(s) are required for somatostatin inhibition of the cyclic AMP generating system, but may not be involved in the PMA potentiation of GRF-stimulated cyclic AMP accumulation.
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PMID:Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin. 287 83

To clarify the precise mechanism by which unrelated peptides, cholecystokinin or carbamylcholine, modulate the somatostatin binding, the effect of a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) or a synthetic diacylglycerol analog, 1-oleyl-2-acetylglycerol (OAG) on [125I-Tyr1]somatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37 degrees C with 100 ng/ml TPA maximally reduced subsequent labeled somatostatin binding to acinar membranes. The inhibitory effect of TPA on the somatostatin binding was dependent on the dose used, or the time and temperature of pretreatment. These effects of TPA were almost mimicked by the treatment of acini with OAG. Scatchard analysis of [125I-Tyr1]somatostatin binding demonstrated that the decrease in the labeled somatostatin binding induced by TPA or OAG pretreatment was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. A specifically labeled single band of the Mr = 90 K obtained with a photoaffinity cross-linking study indicates that the somatostatin binding sites are the same somatostatin receptor as previously described. Moreover, the intensity of the Mr = 90 K band was dramatically decreased when acini were treated with increasing concentrations of TPA, a finding consistent with TPA-induced decrease in binding capacity. Such an inhibitory effect of TPA was abolished when pretreatment of acini with TPA was performed in the presence of Ca2+ chelating compounds such as EDTA and EGTA. Interestingly, the combined treatment of TPA and Ca2+ ionophore A23187 caused synergistic inhibition of the subsequent labeled somatostatin binding to acinar membranes, although Ca2+ ionophore itself almost failed to affect the somatostatin binding. These results suggest, therefore, that TPA or OAG can modulate somatostatin binding to its receptors on rat pancreatic acinar cell membranes, presumably through activation of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) and the activated protein kinase C and intracellular Ca2+ mobilization presumably act to modulate pancreatic acinar somatostatin receptors synergistically.
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PMID:[Phorbol ester or diacylglycerol modulates somatostatin binding to its receptors on rat pancreatic acinar cell membranes]. 287 6

Incubation of cultured ovine pituitary cells with the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) (0.1-100 nM), caused a dose-related stimulation of both growth hormone (ED50 approximately 4 nM) and prolactin (ED50 approximately 14 nM) secretion. Stimulation by TPA (100 nM) produced a substantial 10-fold increase in growth hormone with a smaller, 2-fold rise in prolactin secretion over 30 min; significant effects on the release of both hormones occurred within 2 min. Treatment with TPA also produced a small, time- and concentration-dependent rise in cellular cyclic AMP content which reached, at maximum, a level 20-30% over basal values. Non-tumor-promoting phorbol esters did not stimulate the secretion of either growth hormone or prolactin. In the presence of TPA (10 nM), dopamine (1-1000 nM) suppressed prolactin secretion to a level close to that observed for maximal inhibition of unstimulated cells. At high concentrations (0.1-1.0 microM) dopamine also partially attenuated (by 43%) the TPA-induced stimulation of growth hormone secretion. Somatostatin (0.01-1.0 microM) completely inhibited the substantial (approximately 9-fold) TPA-induced stimulation of growth hormone secretion (inhibitory ED50 approximately 47 nM), and also suppressed TPA-stimulated prolactin secretion to the control level. Our results suggest that activation of protein kinase-C may be involved in the stimulatory regulation of both growth hormone and prolactin secretion in sheep pituitary cells. Failure of TPA to attenuate the inhibitory activity of dopamine and somatostatin suggests that inhibitory regulation occurs at, or beyond, the point in the secretory process regulated by protein kinase-C.
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PMID:Effects of dopamine and somatostatin on phorbol ester-stimulated prolactin and growth hormone secretion. 287 53


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