Endogenous histamine reduces plasma insulin-like growth factor I via H-1 receptor-mediated pathway in the rat

Endotoxin has been recently shown to reduce plasma insulin-like growth fact or I. As it was reported that histamine can induce gut-derived endotoxemia, we wanted to determine whether histamine has a similar effect on plasma in sulin-like growth factor I. Compound 48/80 (a histamine releaser) was injec ted subcutaneously into rats, then blood was taken for plasma insulin-like growth factor I assay and the livers were assayed for insulin-like growth f actor I mRNA. Like endotoxin, injection of compound 48/80 significantly red uced plasma insulin-like growth factor I. Six hours post-injection, plasma insulin-like growth factor I was reduced by 61% (P < 0.001), and 24 h post- injection, it was still lower (by 35% P < 0.001) than in the control group. Hepatic insulin-like growth factor I mRNA was not reduced by this treatmen t, The effect of compound 48/80 on plasma insulin-like growth factor I was significantly attenuated by oral administration of the histamine H-1 recept or antagonist (chlorpheniramine), but not by the histamine Hz receptor anta gonists (cimetidine and ranitidine). Oral administration of polymyxin B (an antiendotoxin antibiotic) did not attenuate the effect of compound 48/80 o n plasma insulin-like growth factor I at all. In conclusion, endogenous his tamine reduces plasma insulin-like growth factor I via H-1 receptor-mediate d pathway. Our study suggests a novel role of histamine in the regulation o f insulin-like growth factor I metabolism in vivo. (C) 1999 Elsevier Scienc e B.V. All rights reserved.