Calapai G, Mazzaglia G, Marciano M C, Squadrito F, Altavilla D, Zingarelli B, Prosdocimi M, Caputi A P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Life Sci. 1992;51(26):2041-8. doi: 10.1016/0024-3205(92)90154-h.
Intravenous (640 micrograms/kg) or intracerebroventricular (0.5 and 1 microgram) injection of Escherichia coli endotoxin (LPS) causes inhibition of water intake induced by 24 hour period of water deprivation in the rat. Tumor necrosis factor alpha (TNF-alpha; 20 and 40 ng/rat) given into the lateral cerebral ventricle (i.c.v.) causes effects similar to those observed after LPS. Cloricromene, given either intravenously (1 and 2 mg/kg) or i.c.v. (250 and 500 ng), abolished the antidipsogenic effect induced by LPS (administered both i.v. and i.c.v.). Cloricromene (2 mg/kg, i.v. or 500 ng/rat, i.c.v.), on the contrary, did not modify the antidipsogenic effects induced by TNF-alpha. These data indicate that peripherally injected cloricromene (as well as that i.c.v. injected) antagonizes the effects of mediators of LPS on sites regulating thirst and suggest that cloricromene's action may be due to inhibition of brain TNF-alpha formation induced by LPS.
静脉注射(640微克/千克)或脑室内注射(0.5微克和1微克)大肠杆菌内毒素(LPS)会抑制大鼠因24小时禁水而引起的饮水。向侧脑室(脑室内注射)注射肿瘤坏死因子α(TNF-α;20纳克/只和40纳克/只)会产生与LPS注射后观察到的类似效果。静脉注射(1毫克/千克和2毫克/千克)或脑室内注射(250纳克和500纳克)氯克罗孟,可消除LPS(静脉注射和脑室内注射)诱导的抗利尿作用。相反,氯克罗孟(2毫克/千克,静脉注射或500纳克/只,脑室内注射)不会改变TNF-α诱导的抗利尿作用。这些数据表明,外周注射(以及脑室内注射)的氯克罗孟可拮抗LPS介质对调节口渴部位的作用,并提示氯克罗孟的作用可能是由于抑制了LPS诱导的脑TNF-α形成。