Histaminergic components in carbachol-induced pituitary-adrenocortical activity.
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.
Institute of Pharmacology, Polish Academy of Sciences, Cracow.
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J
Bugajski
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A
Gadek-Michalska
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J
Borycz
A J
AJ
Bugajski
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R
Głód
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage*; D003345:Corticosterone / Q000097:blood*; D006632:Histamine / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D008762:Methylhistidines / Q000008:administration & dosage; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D006635:Histamine H2 Antagonists; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D002217:Carbachol; D003345:Corticosterone