膵ソマトスタチン受容体の結合特性に関する研究 (第2報):Phorbol ester, 及びDiacylglycerolのラット膵腺房細胞細胞膜へのソマトスタチン結合に及ぼす効果

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To clarify the precise mechanism by which unrelated peptides, cholecystokinin or carbamylcholine, modulate the somatostatin binding, the effect of a phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA) or a synthetic diacylglycerol analog, [125 I-Tyr1-oley1-2-acetylglycerol (OAG) onsomatostatin binding to pancreatic acinar cell membranes was examined. Pretreatment of pancreatic acini for 120 min at 37°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 crosslinking 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 Ca 2+ 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 1) 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 2) the activated protein kinase C and intracellular Ca2+mobilization presumably act to modulate pancreatic acinar somatostatin receptors synergistically.
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膵ソマトスタチン受容体の結合特性に関する研究 (第2報):Phorbol ester, 及びDiacylglycerolのラット膵腺房細胞細胞膜へのソマトスタチン結合に及ぼす効果

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