Tsujimoto S, Kamei C, Yoshida T, Tasaka K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Pharmacology. 1993 Aug;47(2):73-83. doi: 10.1159/000139081.
Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.
研究了脑室注射组胺(H(i))对犬血浆促肾上腺皮质激素(ACTH)和皮质醇水平的影响。以5和10微克/千克的剂量脑室注射H(i)可使血浆ACTH显著升高,而以2 - 10微克/千克的剂量注射H(i)后,血浆皮质醇升高更快且更显著。注射2 - 甲基组胺时也得到了类似结果;在25和50微克/千克的剂量下,血浆ACTH和皮质醇水平均显著升高。然而,即使在50微克/千克的剂量下,4 - 甲基组胺也未引发此类效应。由H(i)或2 - 甲基组胺诱导的血浆皮质醇升高速率明显快于血浆ACTH。吡苄明(脑室注射)与H(i)同时应用可显著抑制H(i)诱导的激素分泌,但西咪替丁进行类似给药时,ACTH和皮质醇均未受影响。在垂体切除的犬中,以5微克/千克的剂量注射H(i)后,血浆皮质醇水平也显著升高。在H(i)注射前后持续静脉输注六甲铵未能抑制H(i)诱导的血浆ACTH和皮质醇水平升高。从这些发现可以得出结论,脑室注射H(i)通过H1受体导致血浆ACTH和皮质醇水平升高,并且表明在某种程度上,H(i)引发的皮质醇释放肯定是在没有ACTH参与的情况下产生的。