Receptor-mediated stimulation of aortic prostacyclin release by 5-hydroxytryptamine

Abstract

5-Hydroxytryptamine (5-HT) stimulated prostacyclin release, measured by radioimmunoassay as 6-keto-prostaglandin F1 alpha, from rat aorta in a dose-dependent manner (3 X 10(-7)-10(-4) M). A statistically significant stimulation was observed at concentrations higher than 3 X 10(-6) M. Norepinephrine also increased prostacyclin release but only at a high concentration (10(-4) M) and histamine (3 X 10(-5) and 10(-4) M) had no significant effect. Among some structurally 5-HT-related analogues, only tryptamine exhibited a dose-dependent stimulatory effect on prostacyclin release but it was slightly less potent than 5-HT. Tryptophan and 5-hydroxytryptophan had no effects whereas 5-hydroxyindoleacetic acid at 10(-4) M stimulated slightly. Prostacyclin release stimulated by 5-HT was depressed by non-specific 5-HT antagonists, methysergide, mianserin and cyproheptadine. In contrast, a specific 5-HT2 antagonist ketanserin (3 X 10(-7)-10(-5) M) had no antagonistic effect. These results suggest that 5-HT stimulates the release of prostacyclin from rat aorta by interaction with receptors distinct from its 5-HT2 subtype.