Neuropharmacological study on central peptidergic regulation of sympatho-adrenomedullary system.

我们最近对蛙皮素引起的中枢抑制胃酸分泌的机制的研究表明，交感神经或肾上腺髓质系统的功能障碍可以被功能不变的系统很好地补偿。然后，脑室注射蛙皮素的作用(i.c.v.)用尿素化大鼠对血浆儿茶酚胺进行神经药理学检测，结果如下。1)Bombein i.c.V.0.3-10nmole剂量依赖性地增加血浆肾上腺素(AD)和去甲肾上腺素(NA)水平[对照组：AD；170±28，NA；429±33pg/ml(n=20)；蛙皮素3nmole后30min：AD；1145±247，NA 719±162 pg/ml(n=50)]。用6-羟基多巴胺化学切断交感神经可明显增强蛙皮素引起的AD水平升高[蛙皮素3nmol后30min；3600±357pg/ml(n=5)]。手术切除肾上腺并不影响蛙皮素诱导的NA水平的升高。2)电刺激蛙皮素的中枢作用部位--视前区，可使去甲肾上腺素和去甲肾上腺素水平升高。3)预先给予α受体阻断剂酚妥拉明(S.C.)，但不加β受体阻滞剂心得安，可加快蛙皮素引起AD而不是NA水平升高的时间。4)静脉注射尼古丁可增加内脏切除大鼠的AD和NA水平。这些结果表明，交感神经系统在AD分泌的调节机制中具有抑制作用。此外，这种调节机制的部位可能位于大脑，而不是外周靶器官，即肾上腺。

From our recent studies on a mechanism of bombesin-induced central inhibition of gastric acid secretion, it was suggested that a dysfunction of the sympathetic or of the adrenomedullary system may well be compensated for by the system with unaltered function. Then, effects of bombesin intracerebroventricularaly applied (i.c.v.) on the plasma levels of catecholamines were neuropharmacoligically examined using urethaneanestetized rats.Results obtained are as follows. 1) Bombesin i.c.v. dose-dependently (0.3-10 nmole) increased plasma levels of adrenaline (AD) and noradrenaline (NA) [Control: AD; 170 + 28, NA; 429 + 33 pg/ml (n=20).Thirty min after 3 nmole of bombesin: AD; 1145 + 247, NA 719 + 162 pg/ml (n=50)]. Chemical sympathitectomy with 6-hydroxydopamine markedly potentiated this bombesin-induced increase in AD level[Thirty min after 3 nmol of bombesin ; 3600 + 357 pg/ml (n=5)]. Surgical adrenalectomy did not affect the bombesin-induced increase in NA level. 2) Electrical stimu-lation of the preoptic area, central site of action of bombesin, increased both the levels of AD and NA as observed with bombesin. 3) Time of appearance of bombesin-induced increase in the level of AD but not of NA was hastened by pretreatment with an alpha-adrenoceptor blockade, phentolamine (s.c.), but not with a beta-adrenoceptor blockade, propranolol. 4) Intravenous infusion of nicotine increased the levels of both AD and NA in the splanchnicectomized rats. This nicotine-induced increases were not modified by chemical sympathitectomy with 6-hydroxydopamine.These results suggest that sympathetic nervous system has an inhibitory role in the regulatory mechanism of AD secretion. Furthermore, sites of this regulatory mechanism is probably resides in the brain but not in the peripheral target organ, adrenal glands.