Liao W, Rudling M, Möller C, Angelin B
Center for Nutrition and Toxicology, NOVUM, Karolinska Institute at Huddinge University Hospital, Sweden.
Eur J Pharmacol. 1999 Jun 25;374(3):471-6. doi: 10.1016/s0014-2999(99)00309-x.
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.
最近研究表明内毒素可降低血浆胰岛素样生长因子I。由于有报道称组胺可诱导肠道源性内毒素血症，我们想要确定组胺对血浆胰岛素样生长因子I是否有类似作用。将化合物48/80（一种组胺释放剂）皮下注射到大鼠体内，然后采集血液进行血浆胰岛素样生长因子I检测，并对肝脏进行胰岛素样生长因子I mRNA检测。与内毒素一样，注射化合物48/80可显著降低血浆胰岛素样生长因子I。注射后6小时，血浆胰岛素样生长因子I降低了61%（P<0.001），注射后24小时，其仍低于对照组（降低了35%，P<0.001）。这种处理并未降低肝脏胰岛素样生长因子I mRNA水平。口服组胺H1受体拮抗剂（氯苯那敏）可显著减弱化合物48/80对血浆胰岛素样生长因子I的作用，但组胺H2受体拮抗剂（西咪替丁和雷尼替丁）则无此作用。口服多粘菌素B（一种抗内毒素抗生素）对化合物48/80降低血浆胰岛素样生长因子I的作用完全没有减弱。总之，内源性组胺通过H1受体介导的途径降低血浆胰岛素样生长因子I。我们的研究提示了组胺在体内胰岛素样生长因子I代谢调节中的新作用。
