Neuropharmacological Studies on the central peptidergic inhibitory mechanism of gastric functions.

我们最近发现，脑室(Icv)给药蛙皮素能兴奋内脏外周神经，从而抑制胃酸分泌。为探讨中枢抑制胃功能的机制，在乌拉坦麻醉下观察蛙皮素和促肾上腺皮质激素释放因子(CRF)对胃功能增强的影响。持续电刺激左侧颈迷走神经(0.5 mA，3次/秒，0.5毫秒)可增强胃功能。结果如下：1)下丘脑视前-前区微量注射蛙皮素3pmole，可抑制刺激引起的胃酸分泌增加。电解破坏该区域可消除蛙皮素(Icv)对胃功能的抑制作用。2)鞘内注射这种多肽，即使大剂量，1000pmole，也不影响刺激诱导的胃酸分泌…的增加更多的CRF icv(0.1、0.3、1.0和3.0pmole)可剂量依赖性地抑制刺激引起的胃酸分泌和粘膜血流量的增加。这种CRF诱导的抑制作用(0.3nmole)在去卵巢动物中未观察到。视前区微量注射CRF(0.1nmole)可抑制刺激引起的胃酸分泌和粘膜血流量的增加。4)电刺激视前区、下丘脑前核和下丘脑室旁核(0.5 mA，10个周期/秒，2毫秒，10分钟)可抑制刺激引起的胃功能增加。这种由这些脑区的激活引起的抑制被先前的内脏切除所消除。5)电刺激视前区外侧2 mm的脑区、下丘脑外侧区对刺激引起的胃功能增加无影响。这些结果表明，起源于下丘脑前部的肽能信息集中地提高交感-肾上腺髓质功能，从而激活胃中的α-肾上腺素能受体，从而抑制胃功能。较少

We have recently found that intracerebroventricular (icv) administration of bombesin excites peripheral splanchnic nerves and a resultant inhibition of gastric acid secretion occurs. To investigate central peptidergic inhibitory mechanism of gastric functions, therefor, effects of bombesin and corticotropin releasing factor (CRF) on enhanced gastric functions were examined in rats under urethane anesthesia. Enhanced gastric functions were induced by continuous electrical stimulation of the left cervical vagus nerve (0.5 mA, 3 cycles/sec, 0.5 msec). Results obtained are as follows: 1) Bombesin, 3 pmole, micro-injected into the preoptic-anterior hypothalamic area inhibited the stimulation-induced increase in gastric acid secretion. Electrolytic destruction of this area abolished the bombesin (icv)-induced inhibition of gastric functions. 2)Intrathecal administration of this peptide even in a large dose, 1,000 pmole, did not affect the stimulation-induced increase in gastric acid secretio … More n. 3) CRF icv applied (0.1, 0.3, 1.0 and 3.0 pmole) dose-dependently inhibited the stimulation-induced increases in gastric acid output and mucosal blood flow. This CRF-induced inhibition (0.3 nmole) was not observed in the splanchinisectimized animals. Microinjection of CRF (0.1 nmole) into the preoptic area inhibited the stimulation-induced increase in gastric acid secretion and mucosal blood flow. 4) Electrical stimulation (0.5 mA, 10 cycles/sec, 2 msec for 10 min) of the preoptic area, the anterior hypothalamic nucleus and the paraventricular nucleus of hypothalamus inhibited the stimulation-induced increases in gastric functions. Such inhibition induced by activation of these brain regions was abolished by prior splanchnisectomy. 5) Electrical stimulation of brain regions 2 mm lateral to the preoptic area, lateral hypothalamic area was without effect on the stimulation-induced increases in gastric functions. These results suggests that peptidergic informations originated from the anterior hypothalamic region centrally elevates sympatho-adrenomedullary functions, and a resultant activation of alpha-adrenoceptors in the stomach inhibits gastric funcitons. Less