It is well recognized that serotonin stimulates aldosterone production by the adrenal glands. To investigate the possible roles of serotonin type 1 and 2 receptors in the regulation of aldosterone production, we examined the effects of cyproheptadine (a serotonin antagonist that inhibits both type 1 and 2 receptors) and ketanserin (a serotonin type 2 selective antagonist) on aldosterone and cAMP production in collagenase dispersed rat adrenal capsular cells. Serotonin, ranging in concentration from 10(-9) to 10(-3) M, significantly increased aldosterone production in a dose-dependent fashion after 2 h of incubation at 37 degrees C. Cyproheptadine and ketanserin showed comparable inhibitory effects on basal aldosterone production. These serotonin antagonists preferentially inhibited serotonin-induced aldosterone production. Serotonin significantly increased cAMP production at a dose of 10(-6) M. Both cyproheptadine and ketanserin significantly decreased basal cAMP production at doses of 10(-5) M. These serotonin antagonists preferentially inhibited serotonin-stimulated cAMP production. These results suggest that adrenal serotonin type 2 receptors may be coupled with adenylate cyclase activity and that these receptors are involved in the regulation of aldosterone production. Whether serotonin plays an important role in the regulation of aldosterone secretion in vivo remains to be elucidated.
