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

Research Project

Project/Area Number	61570107
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	General pharmacology
Research Institution	Kochi Medical School
Principal Investigator	OSUMI Yoshitsugu Kochi Medical School, 医学部, 教授 (80025634)
Project Period (FY)	1986 – 1987
Project Status	Completed (Fiscal Year 1987)
Budget Amount *help	¥1,900,000 (Direct Cost: ¥1,900,000) Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000) Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords	CRF / bombesin / polypeptide / preoptic area / hypothalamus / gastric function / gastric acid secretion / 交感神経-腹腎髄質系 / 胃粘膜血流量 / 外側視床下野 / 視床下部室傍核
Research Abstract	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