Komatsu M, Yokokawa N, Takeda T, Nagasawa Y, Aizawa T, Yamada T
Department of Geriatrics, Endocrinology, and Metabolism, Shinshu University School of Medicine, Nagano-ken, Japan.
Endocrinology. 1989 Oct;125(4):2008-14. doi: 10.1210/endo-125-4-2008.
Pharmacological characteristics of the voltage-dependent calcium channel (VDCC) of the pancreatic B-cell were studied using omega-conotoxin (omega CgTX) and dihydropyridine (DHP) calcium channel blockers. High glucose and potassium (K+) depolarization were employed as the stimulant of insulin release. omega CgTX (greater than 50 nM), a blocker of neural, but not muscular, Ca2+ channels, partially blocked (27%) the second, but not the first, phase of glucose-induced insulin release without a significant effect on K+ depolarization-induced insulin release. The DHP Ca2+ channel blocker nifedipine inhibited both phases of glucose-induced insulin release (ED50 = 200 nM) and completely abolished both phases of response at 10 microM. In contrast, the DHP Ca2+ channel blocker only partially suppressed (75% at 10 microM) K+ depolarization-induced insulin release with an ED50 of 100 nM. We conclude that pancreatic B-cell possesses at least two classes of VDCCs; one is DHP sensitive, and the other DHP insensitive. Partial suppression of the second phase of glucose-induced insulin release by a high concentration of omega CgTX may be due to its toxic effect on the secretory machinery other than VDCC.
使用ω-芋螺毒素（ωCgTX）和二氢吡啶（DHP）钙通道阻滞剂研究了胰腺β细胞电压依赖性钙通道（VDCC）的药理学特性。采用高糖和钾（K+）去极化作为胰岛素释放的刺激因素。ωCgTX（大于50 nM）是神经而非肌肉Ca2+通道的阻滞剂，它部分阻断（27%）葡萄糖诱导的胰岛素释放的第二相，但不影响第一相，且对K+去极化诱导的胰岛素释放无显著影响。DHP钙通道阻滞剂硝苯地平抑制葡萄糖诱导的胰岛素释放的两个阶段（ED50 = 200 nM），并在10 μM时完全消除两个阶段的反应。相比之下，DHP钙通道阻滞剂仅部分抑制（10 μM时为75%）K+去极化诱导的胰岛素释放，ED50为100 nM。我们得出结论，胰腺β细胞至少拥有两类VDCC；一类对DHP敏感，另一类对DHP不敏感。高浓度的ωCgTX对葡萄糖诱导的胰岛素释放第二相的部分抑制可能是由于其对VDCC以外的分泌机制的毒性作用。
