Endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway in the rat.
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.
Liao
W
W
Center for Nutrition and Toxicology, NOVUM, Karolinska Institute at Huddinge University Hospital, Sweden. wliao@bcm.tmc.edu
Rudling
M
M
Möller
C
C
Angelin
B
B
D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D004731:Endotoxins; D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D003189:p-Methoxy-N-methylphenethylamine; D007334:Insulin-Like Growth Factor I; D002927:Cimetidine; D006632:Histamine