Endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway in the rat

Eur J Pharmacol. 1999 Jun 25;374(3):471-6. doi: 10.1016/s0014-2999(99)00309-x.

Abstract

Endotoxin has been recently shown to reduce plasma insulin-like growth factor I. As it was reported that histamine can induce gut-derived endotoxemia, we wanted to determine whether histamine has a similar effect on plasma insulin-like growth factor I. Compound 48/80 (a histamine releaser) was injected subcutaneously into rats, then blood was taken for plasma insulin-like growth factor I assay and the livers were assayed for insulin-like growth factor I mRNA. Like endotoxin, injection of compound 48/80 significantly reduced 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 treatment. The effect of compound 48/80 on plasma insulin-like growth factor I was significantly attenuated by oral administration of the histamine H1 receptor antagonist (chlorpheniramine), but not by the histamine H2 receptor antagonists (cimetidine and ranitidine). Oral administration of polymyxin B (an antiendotoxin antibiotic) did not attenuate the effect of compound 48/80 on plasma insulin-like growth factor I at all. In conclusion, endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway. Our study suggests a novel role of histamine in the regulation of insulin-like growth factor I metabolism in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorpheniramine / pharmacology
  • Cimetidine / pharmacology
  • Endotoxins / pharmacology
  • Histamine / pharmacology
  • Histamine / physiology*
  • Histamine Agonists / pharmacology
  • Histamine H1 Antagonists / pharmacology
  • Histamine H2 Antagonists / pharmacology
  • Histamine Release / drug effects
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Histamine H1 / drug effects
  • Receptors, Histamine H1 / physiology*
  • Signal Transduction*
  • p-Methoxy-N-methylphenethylamine / pharmacology

Substances

  • Endotoxins
  • Histamine Agonists
  • Histamine H1 Antagonists
  • Histamine H2 Antagonists
  • RNA, Messenger
  • Receptors, Histamine H1
  • Chlorpheniramine
  • p-Methoxy-N-methylphenethylamine
  • Insulin-Like Growth Factor I
  • Cimetidine
  • Histamine