Effect of histamine on the secretion of pro-opiomelanocortin derived peptides in rats

Abstract

In conscious male rats intracerebroventricular infusion of histamine increased the plasma concentrations of ACTH and β-endorphin immunoreactivity 2.5-fold (P < 0.01). Gel filtration of plasma revealed two peaks of β-endorphin immunoreactivity corresponding to β-endorphin and β-lipotropin. The two fractions increased almost equally in histamine-stimulated animals, whereas most of the circulating β-endorphin immunoreactivity in control animals corresponded to β-endorphin. Central infusion of the H₁-receptor agonist 2-thiazolylethylamine and of the H₂-receptor agonists dimaprit or 4-methylhistamine increased the plasma ACTH and β-endorphin immunoreactivity concentrations 2- and 3-fold, respectively (P < 0.01). Infused intracerebroventricularly, the H₂-receptor antagonists cimetidine or ranitidine prevented the histamine-induced increase in plasma ACTH and β-endorphin immunoreactivity (P < 0.01), whereas the H₁-receptor antagonist mepyramine inhibited the peptide responses by 70% (P < 0.01). Infused intra-arterially cimetidine or ranitidine inhibited the histamine-induced increase in plasma ACTH by 80% (P < 0.01) and plasma β-endorphin immunoreactivity by 45% (P < 0.05), whereas mepyramine or the other H₁-receptor antagonist SKF-93944 inhibited the ACTH response by 50% (P < 0.05), but had no effect on the β-endorphin immunoreactivity. The results indicate that histamine increases the release of the pro-opiomelanocortin derived peptides ACTH, β-lipotropin and β-endorphin from the anterior pituitary lobe, whereas an effect of histamine on the release of β-endorphin from the neurointermediate lobe is possible. The effect of histamine seems primarily mediated by H₂-receptors, whereas H 1-receptors appear to play a minor role.