Hurst R D, Chan S L, Morgan N G
Department of Biological Sciences, University of Keele, Staffordshire.
J Mol Endocrinol. 1989 Mar;2(2):99-105. doi: 10.1677/jme.0.0020099.
Insulin secretion from isolated rat islets of Langerhans in the presence of 4 mM glucose averaged 2.26 +/- 0.20 (S.E.M.) ng/islet per 90 min and was significantly (P less than 0.001; n = 30) increased to 3.28 +/- 0.21 ng/islet per 90 min by the covalent alpha-adrenoceptor antagonist benextramine (10 microM). Glucose (20 mM) also increased the secretion rate (to 6.24 +/- 6.0 ng/islet per 90 min) but, under these conditions, the response was not further enhanced by benextramine. Clonidine and noradrenaline (1 nM-10 microM) each caused dose-dependent inhibition of glucose-induced insulin secretion which was maximal at 1 microM. Benextramine, when added simultaneously with the agonist, relieved, in a dose-dependent manner, the inhibition of secretion induced by either clonidine or noradrenaline with similar sensitivity. Even after a 30-min preincubation with benextramine the antagonist failed to differentiate between noradrenaline, adrenaline and clonidine with respect to inhibition of insulin secretion. In contrast to its effects on adrenergic responses, short-term treatment with benextramine did not significantly affect muscarinic-cholinergic receptor-mediated 45Ca2+ efflux from rat islets of Langerhans perifused in Ca2+-depleted medium. These data suggest that benextramine does not differentiate between clonidine and noradrenaline in rat islets of Langerhans but that it does show preference for alpha-adrenoceptors in this tissue.
在4 mM葡萄糖存在的情况下，分离的大鼠胰岛的胰岛素分泌平均为每90分钟2.26±0.20（标准误）ng/胰岛，共价α-肾上腺素能受体拮抗剂苄胺（10 microM）使其显著增加（P<0.001；n = 30）至每90分钟3.28±0.21 ng/胰岛。葡萄糖（20 mM）也增加了分泌率（至每90分钟6.24±6.0 ng/胰岛），但在这些条件下，苄胺并未进一步增强该反应。可乐定和去甲肾上腺素（1 nM - 10 microM）均引起剂量依赖性抑制葡萄糖诱导的胰岛素分泌，在1 microM时达到最大抑制。当与激动剂同时添加时，苄胺以剂量依赖性方式缓解了可乐定或去甲肾上腺素诱导的分泌抑制，敏感性相似。即使在与苄胺预孵育30分钟后，拮抗剂在抑制胰岛素分泌方面仍无法区分去甲肾上腺素、肾上腺素和可乐定。与其对肾上腺素能反应的影响相反，苄胺的短期处理并未显著影响在缺钙培养基中灌流的大鼠胰岛中由毒蕈碱 - 胆碱能受体介导的45Ca2+外流。这些数据表明，苄胺在大鼠胰岛中无法区分可乐定和去甲肾上腺素，但在该组织中确实对α-肾上腺素能受体表现出偏好。
