Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures

Abstract

Calogero AE, Bagdy G, Burrello N, Polosa P. D'Agata R. Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures. Eur J Endocrinol 1995;133:251–4. ISSN 0804–4643 Although several serotonin (5-HT) receptor types have been shown capable of stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, relatively little is known about the role of the 5-HT3 receptor, a receptor that has generated a great deal of interest for its involvement in many behavioral and therapeutic effects. Hence, in this study, we tested the effects of the 5-HT¾ receptor antagonist 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 pituitary cells. Subsequently, we evaluated the effects of the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-stimulated 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 72222, suggesting that 5-HT stimulates basal ACTH release through activation of 5-HT3 receptors. Accordingly, m-CPBG stimulated basal ACTH release 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 ACTH from the pituitary gland in vitro. Aldo E Calogero, Istituto di Clinica Medica I, Ospedale Garibaldi, Piazza S Maria di Gesú, 95123 Catania, Italy