Bugajski J, Gadek-Michalska A, Borycz J, Bugajski A J, Głód R
Institute of Pharmacology, Polish Academy of Sciences, Cracow.
J Physiol Pharmacol. 1994 Sep;45(3):419-28.
The involvement of central histaminergic mechanisms in stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by carbachol, a muscarinic cholinergic agonist, was investigated in conscious rats. The HPA activity was assessed indirectly, through corticosterone secretion. Carbachol given intracerebroventricularly elicited a dose-related increase in serum corticosterone levels. The corticosterone response to carbachol was totally abolished by systemic pretreatment 2h earlier with alpha-fluoro-methylhistidine (alpha-FMH), a specific inhibitor of brain histamine synthesis, which also significantly decreased histamine level in hypothalamus. Mepyramine, a histamine H1-receptor antagonist, moderately diminished the carbachol-induced corticosterone response and abolished the rise in hypothalamic histamine levels. Ranitidine a H2-receptor antagonist, considerably diminished the corticosterone response to carbachol but did not change the elevated hypothalamic histamine levels. Also atropine, a cholinergic antagonist, abolished the corticosterone response to carbachol, but did not significantly affect the carbachol-induced increase in hypothalamic histamine concentration. Ranitidine and atropine can directly block homologous hypothalamic receptors involved in CRF secretion. Partial inhibition of the carbachol-induced corticosterone secretion by mepyramine may be connected with prevention of the carbachol-induced increase in hypothalamic histamine content. These results suggest that hypothalamic histamine and histamine receptors are involved in the HPA stimulation by the muscarinic agonist carbachol.
在清醒大鼠中，研究了中枢组胺能机制在毒蕈碱胆碱能激动剂卡巴胆碱刺激下丘脑 - 垂体 - 肾上腺（HPA）轴中的作用。通过皮质酮分泌间接评估HPA活性。脑室内注射卡巴胆碱可引起血清皮质酮水平呈剂量相关的升高。在2小时前用α-氟甲基组氨酸（α-FMH）进行全身预处理可完全消除对卡巴胆碱的皮质酮反应，α-FMH是一种脑组胺合成的特异性抑制剂，它还显著降低了下丘脑的组胺水平。组胺H1受体拮抗剂美吡拉敏适度减弱了卡巴胆碱诱导的皮质酮反应，并消除了下丘脑组胺水平的升高。H2受体拮抗剂雷尼替丁显著减弱了对卡巴胆碱的皮质酮反应，但并未改变下丘脑升高的组胺水平。同样，胆碱能拮抗剂阿托品消除了对卡巴胆碱的皮质酮反应，但并未显著影响卡巴胆碱诱导的下丘脑组胺浓度升高。雷尼替丁和阿托品可直接阻断参与促肾上腺皮质激素释放因子（CRF）分泌的同源下丘脑受体。美吡拉敏对卡巴胆碱诱导的皮质酮分泌的部分抑制可能与防止卡巴胆碱诱导的下丘脑组胺含量增加有关。这些结果表明，下丘脑组胺和组胺受体参与了毒蕈碱激动剂卡巴胆碱对HPA的刺激。
