Garcia-Morales P, Dufrane S P, Sener A, Valverde I, Malaisse W J
Biosci Rep. 1984 Jun;4(6):511-21. doi: 10.1007/BF01122227.
Conflicting opinions were recently expressed concerning the possible effect of alpha 2-adrenergic agonists upon cyclic AMP production in pancreatic islets. In the present study, clonidine inhibited glucose-induced insulin release from rat pancreatic islets, this inhibitory effect being abolished by idazoxan. Clonidine did not suppress the capacity of forskolin to augment glucose-induced insulin release. In a particulate subcellular fraction derived from the islets, adenylate cyclase was activated by calmodulin (in the presence of Ca2+), NaF, GTP, L-arginine, and forskolin, and slightly inhibited by clonidine. The inhibitory action of clonidine upon basal adenylate cyclase activity was more pronounced in islet crude homogenates. The inhibitory effect of clonidine was antagonized by forskolin whether in the particulate fraction or crude homogenate. At variance with the modest effects of glucagon, D-glucose, L-arginine, or a tumor-promoting phorbol ester upon cyclic AMP production by intact islets, forskolin caused a six-fold increase in cyclic AMP production. Clonidine inhibited cyclic AMP production by intact islets, whether in the absence or presence of forskolin. It is proposed that the inhibitory action of clonidine upon insulin release is attributable, in part at least, to inhibition of adenylate cyclase.
最近，关于α2-肾上腺素能激动剂对胰岛中环磷酸腺苷（cAMP）生成的可能影响，出现了相互矛盾的观点。在本研究中，可乐定抑制了大鼠胰岛中葡萄糖诱导的胰岛素释放，而这种抑制作用被咪唑克生消除。可乐定并未抑制福斯可林增强葡萄糖诱导的胰岛素释放的能力。在来自胰岛的微粒体亚细胞组分中，腺苷酸环化酶被钙调蛋白（在Ca2+存在下）、氟化钠、鸟苷三磷酸（GTP）、L-精氨酸和福斯可林激活，并被可乐定轻微抑制。可乐定对基础腺苷酸环化酶活性的抑制作用在胰岛粗匀浆中更为明显。无论在微粒体组分还是粗匀浆中，福斯可林都能拮抗可乐定的抑制作用。与胰高血糖素、D-葡萄糖、L-精氨酸或促肿瘤佛波酯对完整胰岛cAMP生成的适度影响不同，福斯可林使cAMP生成增加了六倍。无论是否存在福斯可林，可乐定均抑制完整胰岛的cAMP生成。有人提出，可乐定对胰岛素释放的抑制作用至少部分归因于对腺苷酸环化酶的抑制。
