膵腺房細胞Somatostatin受容体特性に関する研究

-第一報-C端octapeptide CCK, carbachol前処理のsomatostatin結合抑制効果

抄録

Somatostatin binding to its receptors on rat pancreatic acinar membranes was characterized with [¹²⁵I-Tyr¹ somatostatin. The COOH-terminal octapeptide of cholecystokinin (CCK8), when present at various concentrations in the reaction mixture for the binding study, reduced labeled somatostatin binding in a dose-dependent manner, whereas carbachol or Ca²⁺ ionophore did not affect the binding. By contrast, when pancreatic acini were first treated with carbachol and thereafter [¹²⁵I-Tyr¹ somatostatin binding to membranes prepared from these acini was examined, carbachol reduced subsequent somatostatin binding in a dose-dependent manner. Scatchard analysis of the labeled somatostatin binding revealed that carbachol pretreatment decreased the maximum binding capacity from 142±20 fmol/ mg of membrane protein to 63.5±3.5 fmol/mg of membrane protein without significantly affecting the binding affinity. To test for the possibility that CCK₈ also may affect labeled somatostatin binding through an intracellular process, pancreatic acini were first treated with CCK₈ and then the membrane bound CCK₈ was washed out. Subsequent labeled somatostatin binding to membranes from these acini was also decreased. When 1 mM EDTA was present in the pretreatment medium, the inhibitory effect of carbachol or CCK₈ was partially abolished, suggesting that an intracellular process to modulate somatostatin binding is dependent on Ca²⁺. On the other hand, pretreatment of acini with Ca²⁺ionophore almost failed to affect subsequent labeled somatostatin binding.
Results therefore suggest that 1) CCK₈ can modulate labeled somatostatin binding to pancreatic acinar membranes not only acting through an intracellular process but also at membrane sites and 2) carbachol-or CCK₈-activated intracellular process to modulate somatostatin binding is dependent on Ca²⁺, but Ca²⁺mobilization itself is not sufficient to affect subsequent somatostatin binding.