Yokotani K, Yokotani K, Okuma Y, Osumi Y
Department of Pharmacology, Kochi Medical School, Japan.
J Pharmacol Exp Ther. 1988 Jan;244(1):335-40.
Mechanisms related to the gastric antisecretory action of i.c.v.-administered prostaglandins (PGs) were investigated in urethane-anesthetized rats with gastric fistula. The gastric acid output was enhanced by electrical stimulation of the left cervical vagus nerve after cutting the bilateral cervical vagus nerves. Intracerebroventricular administered PGE2 (0.05-0.5 microgram/animal) dose-dependently inhibited the vagally stimulated acid output whereas the same doses of PGE2 administered i.v. were without effect. The inhibitory effect of PGE2 (0.1 microgram/animal, i.c.v.) was more potent than the effects of the same doses of PGD2 and PGF2 alpha (PGE2 greater than PGD2 greater than PGF2 alpha). PGE2 (0.1 microgram/animal)-induced inhibition of the gastric acid output was abolished by splanchnicectomy, cutting the preganglionic splanchnic nerves under diaphragm, or by combined pretreatment with adrenalectomy and 6-hydroxydopamine (50 mg/kg i.v., 3 days before). This PGE2-induced inhibition was also abolished by pretreatment with phentolamine (5 mg/kg i.m.), but not by propranolol (5 mg/kg i.m.). These observations suggest that the i.c.v.-administered PGs, in particular PGE2, induces a central excitation of the sympathoadrenomedullary outflow and that the resultant activation of gastric alpha adrenoceptors inhibits the vagally stimulated gastric acid output.
在患有胃瘘的氨基甲酸乙酯麻醉大鼠中，研究了脑室内注射前列腺素（PGs）的胃抗分泌作用相关机制。切断双侧颈迷走神经后，通过电刺激左侧颈迷走神经来增强胃酸分泌。脑室内注射PGE2（0.05 - 0.5微克/只动物）剂量依赖性地抑制迷走神经刺激引起的胃酸分泌，而静脉注射相同剂量的PGE2则无作用。PGE2（0.1微克/只动物，脑室内注射）的抑制作用比相同剂量的PGD2和PGF2α更强（PGE2＞PGD2＞PGF2α）。通过内脏神经切除术、切断膈下的内脏神经节前神经或联合肾上腺切除术和6 - 羟基多巴胺（静脉注射50毫克/千克，术前3天）预处理，可消除PGE2（0.1微克/只动物）诱导的胃酸分泌抑制。用酚妥拉明（肌肉注射5毫克/千克）预处理也可消除这种PGE2诱导的抑制作用，但普萘洛尔（肌肉注射5毫克/千克）预处理则不能。这些观察结果表明，脑室内注射的PGs，特别是PGE2，可诱导交感肾上腺髓质传出神经的中枢兴奋，由此产生的胃α肾上腺素能受体激活可抑制迷走神经刺激引起的胃酸分泌。
