Angel I, Bidet S, Langer S Z
Department of Biology, Laboratoires d'Etudes et de Recherches Synthelabo, Paris, France.
J Pharmacol Exp Ther. 1988 Sep;246(3):1098-103.
The selective alpha-2 adrenoceptor agonist UK 14.304 induced in the mouse a dose-dependent hyperglycemic response which was accompanied by a concomitant inhibition of insulin secretion. Similar effects were observed with the preferential alpha-2 receptor agonists clonidine and guanabenz whereas less pronounced effects were found with (-)-epinephrine. No significant effects on blood glucose levels were observed with the alpha-1 adrenoceptor agonist methoxamine. Adrenalectomy or depletion of catecholamine stores by reserpine, alpha-methylparatyrosine or DSP4 failed to modify the hyperglycemic response to UK 14.304. However, streptozotocin diabetic mice did not respond to UK 14.304. The hyperglycemia induced by submaximal doses of UK 14.304 was antagonized by the centrally and peripherally acting alpha-2 adrenoceptor antagonists rauwolscine, yohimbine, idazoxan and phentolamine, by the peripheral antagonist benextramine but not by prazosin (alpha-1 selective) or propranolol (beta adrenergic). Thus, it may be suggested that the alpha agonist-induced hyperglycemia is mediated via postsynaptic alpha-2 adrenoceptors located on pancreatic beta cells and that it is mediated through the inhibition of insulin secretion.
选择性α-2肾上腺素能受体激动剂UK 14.304在小鼠中诱导出剂量依赖性的高血糖反应，同时伴有胰岛素分泌的抑制。在优先α-2受体激动剂可乐定和胍那苄中也观察到类似的效果，而在（-）-肾上腺素中观察到的效果则不太明显。α-1肾上腺素能受体激动剂甲氧明对血糖水平没有显著影响。肾上腺切除术或用利血平、α-甲基对酪氨酸或DSP4消耗儿茶酚胺储备未能改变对UK 14.304的高血糖反应。然而，链脲佐菌素糖尿病小鼠对UK 14.304没有反应。次最大剂量的UK 14.304诱导的高血糖被中枢和外周作用的α-2肾上腺素能受体拮抗剂萝芙木碱、育亨宾、咪唑克生和酚妥拉明、外周拮抗剂苯苄胺拮抗，但不被哌唑嗪（α-1选择性）或普萘洛尔（β肾上腺素能）拮抗。因此，可以认为α激动剂诱导的高血糖是通过位于胰腺β细胞上的突触后α-2肾上腺素能受体介导的，并且是通过抑制胰岛素分泌介导的。
