Carlisle M A, Smyth D D, Glavin G B
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Pharmacol Exp Ther. 1995 Aug;274(2):598-601.
I1-imidazoline receptor activation by moxonidine has potent antigastric secretory and gastroprotective effects in rats. We therefore tested whether an imidazoline receptor antagonist, efaroxan, would influence gastric secretion and block the antisecretory and antiulcer effects of moxonidine. When given intracerebroventricularly (i.c.v.), moxonidine inhibited basal acid output in conscious rats to a maximum of 38%. Moxonidine given i.p. also significantly increased gastric adherent mucus levels in rats subjected to cold-restraint stress. Efaroxan alone given i.c.v., did not influence gastric secretion nor did it affect moxonidine's ability to decrease gastric secretion. Similarly, peripherally administered efaroxan did not block the antisecretory effect of moxonidine given i.c.v. However, when both compounds were given i.p., efaroxan pretreatment at all but the lowest doses significantly blocked the antigastric secretory effect of moxonidine. Efaroxan alone (i.p.) did not influence stress-induced gastric mucosal injury or adherent mucus levels. However, pretreatment of rats with efaroxan i.p. significantly blocked the mucus-preserving effect of i.p. moxonidine. These results demonstrate that central (i.c.v.) or peripheral (i.p.) administration of the I1-imidazoline receptor agonist moxonidine is associated with gastroprotection. The ability of i.p. efaroxan to block the effects of i.p. moxonidine but not i.c.v. moxonidine indicates that imidazoline receptors located centrally and peripherally may represent two unique sites associated with gastroprotection.
莫索尼定激活I1-咪唑啉受体对大鼠具有强大的抗胃酸分泌和胃保护作用。因此，我们测试了一种咪唑啉受体拮抗剂依发洛新是否会影响胃酸分泌，并阻断莫索尼定的抗分泌和抗溃疡作用。当脑室内注射（i.c.v.）时，莫索尼定可将清醒大鼠的基础酸分泌抑制达38%。腹腔注射（i.p.）莫索尼定也可显著增加遭受冷束缚应激大鼠的胃黏膜黏附黏液水平。单独脑室内注射依发洛新不影响胃酸分泌，也不影响莫索尼定降低胃酸分泌的能力。同样，外周给予依发洛新也不阻断脑室内注射莫索尼定的抗分泌作用。然而，当两种化合物均腹腔注射时，除最低剂量外，依发洛新预处理均显著阻断了莫索尼定的抗胃酸分泌作用。单独腹腔注射依发洛新不影响应激诱导的胃黏膜损伤或黏附黏液水平。然而，腹腔注射依发洛新预处理大鼠可显著阻断腹腔注射莫索尼定的黏液保护作用。这些结果表明，中枢（i.c.v.）或外周（i.p.）给予I1-咪唑啉受体激动剂莫索尼定均具有胃保护作用。腹腔注射依发洛新可阻断腹腔注射莫索尼定的作用，但不能阻断脑室内注射莫索尼定的作用，这表明中枢和外周的咪唑啉受体可能代表与胃保护相关的两个独特位点。
