Tsoli E, Chan S L, Morgan N G
Department of Biological Sciences, Keele University, Staffs, UK.
Eur J Pharmacol. 1995 Sep 15;284(1-2):199-203. doi: 10.1016/0014-2999(95)00455-t.
In order to study the pharmacology of the putative imidazoline receptor involved in stimulation of insulin secretion, the potent and selective imidazoline I1 receptor agonist, moxonidine, was employed. Surprisingly, this agent caused a rapid and complete inhibition of glucose-induced insulin secretion in isolated rat islets of Langerhans. This response was reversible upon removal of the compound but was only partially attenuated under conditions of complete alpha 2 blockade, suggesting that it did not derive entirely from the weak alpha 2-adrenoceptor agonist activity of moxonidine. Furthermore, the response could not be attributed to activation of imidazoline I1 receptors since it was not reproduced by a second potent imidazoline I1 receptor agonist, cimetidine, and could not be alleviated by the imidazoline I1 receptor antagonist efaroxan. The results confirm that the imidazoline receptor involved in control of insulin secretion differs from the I1 subclass and suggest that moxonidine inhibits insulin secretion by a mechanism unrelated to imidazoline I1 receptor agonism.
为了研究参与刺激胰岛素分泌的假定咪唑啉受体的药理学特性，使用了强效且选择性的咪唑啉I1受体激动剂莫索尼定。令人惊讶的是，该药物在分离的大鼠胰岛中引起了葡萄糖诱导的胰岛素分泌的快速且完全抑制。去除该化合物后，这种反应是可逆的，但在完全α2阻断的条件下仅部分减弱，这表明它并非完全源自莫索尼定微弱的α2肾上腺素能受体激动剂活性。此外，该反应不能归因于咪唑啉I1受体的激活，因为第二种强效咪唑啉I1受体激动剂西咪替丁未重现该反应，且咪唑啉I1受体拮抗剂依发洛新也无法缓解该反应。结果证实，参与胰岛素分泌控制的咪唑啉受体不同于I1亚类，并表明莫索尼定通过与咪唑啉I1受体激动作用无关的机制抑制胰岛素分泌。
