ROLE FOR SEROTONIN(3) RECEPTORS IN THE CONTROL OF ADRENOCORTICOTROPICHORMONE-RELEASE FROM RAT PITUITARY CELL-CULTURES

Although several serotonin (5-HT) receptor types have been shown capab le of stimulating the release of adrenocorticotropic hormone (ACTH) fr om the pituitary gland, relatively little is known about the role of t he 5-HT3 receptor, a receptor that has generated a great deal of inter est for its involvement in many behavioral and therapeutic effects. He nce, in this study, we tested the effects of the 5-HT3/4 receptor anta gonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) and the selective 5-HT3 receptor antagonist 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) on ACTH release stimulated by 5-HT from primary cultures of rat pitui tary cells. Subsequently, we evaluated the effects of the selective 5- HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, c orticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-s timulated ACTH release. The maximal stimulatory effect of 5-HT (10(-9) mol/l) on ACTH release was antagonized by both ICS 205-930 and MDL 72 222, suggesting that 5-HT stimulates basal ACTH release through activa tion of 5-HT3 receptors. Accordingly, m-CPBG stimulated basal ACTH rel ease in a concentration-dependent fashion. In contrast to 5-HT, m-CPBG did not have any effect on CRH-stimulated ACTH release and inhibited AVP-stimulated ACTH release in a concentration-dependent manner. These data suggest that the 5-HT3 receptor is involved in the release of AC TH from the pituitary gland in vitro.