INVESTIGATION OF THE ROLE OF 5-HT3 RECEPTORS IN THE SECRETION OF PROLACTIN, ACTH AND RENIN

The potential roles of central and peripheral 5-HT3 receptors in the s ecretion of prolactin, adrenocorticotropic hormone (ACTH), corticoster one and renin was investigated. Male rats received the 5-HT3 antagonis t ondansetron (0, 0.1 or 1 mg/kg i.p.), 30 min prior to injections of the serotonin (5-HT) releaser, p-chloroamphetamine (PCA; 0, 3 or 8 mg/ kg i.p.). Blood samples were collected 60 min after PCA for radioimmun oassays of plasma prolactin, ACTH, corticosterone and renin concentrat ions. PCA significantly elevated secretion of each of these hormones. Pretreatment with the 5-HT3 antagonist, ondansetron, significantly att enuated the PCA-induced elevation of prolactin secretion, suggesting t hat 5-HT3 receptors contribute to the serotonergic stimulation of prol actin secretion. Ondansetron did not modify effects of PCA on ACTH, co rticosterone or renin secretion. To determine whether the 5-HT3 recept or role in prolactin secretion is mediated in the brain, the endocrine effects of intracerebroventricular (i.c.v.) injections of 5-HT (30 mu /kg) or the 5-HT3 agonist, 2-methylserotonin (1, 20 or 200 mu/kg) were evaluated. Both 5-HT and 2-methylserotonin significantly elevated pla sma prolactin levels 15 min postinjection. However, ondansetron (1 mg/ kg i.p.) did not antagonize these actions. Both 5-HT and 2-methylserot onin also increased plasma ACTH and corticosterone concentrations. Fin ally, 5-HT suppressed, while 2-methylserotonin stimulated renin secret ion. None of the hormonal effects of i.c.v. injected 5-HT or 2-methyls erotonin were altered by ondansetron. Thus, the results suggest that p eripheral, but not central 5-HT3 receptors are involved in the stimula tion of prolactin secretion. Furthermore, 5-HT3 receptors do not media te the serotonergic stimulation of ACTH, corticosterone, or renin secr etion.