Effects of H2-receptor antagonists on prolactin secretion: Specificity and mediation of the response

Abstract

Abstract. The effects on prolactin secretion of histamine H2-receptor antagonists infused intracerebroventricularly were studied in urethane anaesthetized male rats. A dose of 1.6 μmol cimetidine stimulated basal prolactin secretion and did not affect the histamine-induced release, whereas 0.4 μmol cimetidine inhibited basal and histamine-stimulated prolactin secretion. 0.1 μmol cimetidine had no effect. The more potent H2-receptor antagonist ranitidine at doses of 0.1, 0.4, 1.6 μmol had no effect on basal prolactin secretion, whereas 0.4 and 1.6 μmol inhibited the histamine-stimulated secretion completely. SKF-92408, a compound resembling cimetidine in chemical structure but devoid of H2-receptor antagonist activity, stimulated basal prolactin secretion at a dose of 1.6 μmol, but had no effect on the histamine-induced release or at a dose of 0.4 μmol. The H2-receptor antagonists metiamide and oxmetidine (1.6 μmol) stimulated basal prolactin secretion and did not prevent the response to histamine. A dose of 0.4 or 1.6 μmol imidazole (the ring structure contained in cimetidine, SKF-92408, metiamide, and oxmetidine) had no effect on basal or histamine-stimulated prolactin secretion. The findings indicate that cimetidine stimulates prolactin secretion by a non-specific action when infused centrally at high doses. In contrast, when infused at lower doses cimetidine inhibits the basal and histamine-stimulated secretion by blockade of H2-receptors. The prolactin-stimulatory action of cimetidine was not due to an H2-agonist effect, since ranitidine did not prevent the response. Cimetidine did not stimulate prolactin secretion via an effect on the dopaminergic system, since the drug had no effect on the dopamine concentration in hypophysial portal blood or in hypothalamic tissue and since inhibition of the dopamine synthesis by α-methyl-p-tyrosine did not prevent the cimetidine-induced prolactin release.