Müllner K, Gyires K, Furst S
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Faculty of Medicine, Budapest 1445 POB 370, Hungary.
J Physiol Paris. 2001 Jan-Dec;95(1-6):209-14. doi: 10.1016/s0928-4257(01)00027-4.
The aim of the present study was to analyse the role of the central alpha-2 adrenoceptors in the regulation of gastric acid secretion in pylorus ligated rats. It was found that the intracerebroventricularly (icv.) injected presynaptic alpha-2 adrenoceptor agonist clonidine and the alpha-2A adrenoceptor subtype selective stimulant oxymetazoline exerted a dose dependent inhibition on gastric acid secretion. The antisecretory ED(50) values for clonidine and oxymetazoline were 20 and 7.5 nmol/rat icv., respectively. The antisecretory effect of these compounds was antagonised by the presynaptic adrenoceptor antagonist yohimbine (50 nmol/rat icv.) indicating that the action is mediated through central presynaptic alpha-2 adrenoceptors. Moreover, naloxone (50 nmol/rat icv.)--non-selective opioid antagonist--and naltrindole (0.5 nmol/rat icv.)--delta-opioid receptor selective antagonist--also decreased the antisecretory effect of clonidine and oxymetazoline suggesting that the endogenous opioid system is likely to be involved in the central antisecretory action of alpha-2 adrenoceptor stimulants.
本研究的目的是分析中枢α-2肾上腺素能受体在幽门结扎大鼠胃酸分泌调节中的作用。研究发现,脑室内(icv.)注射的突触前α-2肾上腺素能受体激动剂可乐定和α-2A肾上腺素能受体亚型选择性兴奋剂奥昔麻黄碱对胃酸分泌具有剂量依赖性抑制作用。可乐定和奥昔麻黄碱的抗分泌ED(50)值分别为20和7.5 nmol/大鼠icv.。这些化合物的抗分泌作用被突触前肾上腺素能受体拮抗剂育亨宾(50 nmol/大鼠icv.)拮抗,表明该作用是通过中枢突触前α-2肾上腺素能受体介导的。此外,纳洛酮(50 nmol/大鼠icv.)——非选择性阿片受体拮抗剂——和纳曲吲哚(0.5 nmol/大鼠icv.)——δ-阿片受体选择性拮抗剂——也降低了可乐定和奥昔麻黄碱的抗分泌作用,提示内源性阿片系统可能参与α-2肾上腺素能受体兴奋剂的中枢抗分泌作用。