Involvement of histaminergic neurons in the stress-induced release of pro-opiomelanocortin-derived peptides in rats.

Histamine, which acts as a neurotransmitter, stimulates the release of the pro-opiomelanocortin derived peptides ACTH, beta-lipotropin, and beta-endorphin. Since stress affects the hypothalamic turn-over of neuronal histamine, we investigated the role of histaminergic neurons in the mediation of the stress-induced release of ACTH and beta-endorphin immunoreactivity in male rats. In control animals histamine receptor antagonists had no effect on the release of ACTH or beta-endorphin immunoreactivity. Restraint and ether stress increased plasma ACTH 3- and 2-fold, respectively. The responses were almost prevented by intracerebroventricular or intra-arterial infusion of the H2-receptor antagonists cimetidine and ranitidine. Infused intracerebroventricularly the H1-receptor antagonist mepyramine inhibited the ACTH response to restraint by 45% (P less than 0.01), but had no effect on the response to ether. Infused intra-arterially the H1-receptor antagonists mepyramine or SKF-93944 had no effect. Restraint and ether stress increased plasma beta-endorphin immunoreactivity 6- and 5-fold, respectively. Sephadex G-50 gel chromatography of plasma showed that the beta-endorphin immunoreactivity in stressed rats co-eluted with beta-lipotropin and beta-endorphin, whereas the immunoreactivity in control animals co-eluted almost exclusively with beta-endorphin. The H2-receptor antagonists cimetidine and ranitidine infused intracerebroventricularly inhibited the responses of beta-endorphin immunoreactivity to restraint and ether stress by 90 and 70%, respectively, whereas intra-arterial infusion of these antagonists inhibited the responses by only 50 and 60%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)