Hsu H C, Flancbaum L J, Kasziba E, Merrill G F, Fisher H
Department of Nutritional Science, Rutgers University, New Brunswick, New Jersey 08903.
Dig Dis Sci. 1991 Dec;36(12):1708-14. doi: 10.1007/BF01296614.
In this investigation, an isolated, perfused rat stomach system was used to elucidate the roles of histamine, serotonin, and the action of cimetidine, methysergide, and propranolol in relation to the in vivo and in vitro administration of compound 48/80. While histamine administered both in vivo and in vitro stimulated acid secretion in the perfused rat stomach, serotonin, added in vitro, inhibited histamine-induced gastric acid secretion. Cimetidine, given either in vivo or in vitro, blocked histamine-induced acid secretion, and methysergide, but not propranolol, reversed the serotonin-induced inhibition of histamine-stimulated acid secretion. Compound 48/80, given in vitro, caused gastric acid secretion that was blocked by pretreatment with cimetidine. Administered in vivo, however, compound 48/80 inhibited both basal and histamine-stimulated acid secretion. This inhibition was partially reversed by pretreatment with methysergide. The absence of inhibition of acid secretion by in vitro-administered compound 48/80 may be related to the timing of the serotonin effect. When serotonin was given prior to histamine, it blocked acid secretion, whereas no inhibition occurred when serotonin was administered together with histamine. None of the other agents investigated affected basal acid secretion.
在本研究中,使用离体灌注大鼠胃系统来阐明组胺、5-羟色胺以及西咪替丁、甲基麦角新碱和普萘洛尔的作用与化合物48/80体内和体外给药的关系。虽然体内和体外给予组胺均刺激了灌注大鼠胃中的胃酸分泌,但体外添加的5-羟色胺抑制了组胺诱导的胃酸分泌。体内或体外给予西咪替丁均阻断了组胺诱导的胃酸分泌,甲基麦角新碱而非普萘洛尔逆转了5-羟色胺诱导的对组胺刺激胃酸分泌的抑制作用。体外给予化合物48/80会引起胃酸分泌,而西咪替丁预处理可阻断这种分泌。然而,体内给予化合物48/80会抑制基础胃酸分泌和组胺刺激的胃酸分泌。甲基麦角新碱预处理可部分逆转这种抑制作用。体外给予化合物48/80时无胃酸分泌抑制作用可能与5-羟色胺作用的时间有关。当5-羟色胺先于组胺给药时,它会阻断胃酸分泌,而当5-羟色胺与组胺同时给药时则无抑制作用。所研究的其他药物均未影响基础胃酸分泌。