Extracellular serotonin promotes melatonin release from cultured rat pinealocytes: evidence for an S2-type receptor-mediated autocrine feedback.

Recent evidence points to the secretion of serotonin from the rat pineal gland both in vivo and in vitro. In view of the fact that adrenergic stimulation of cultured pinealocytes leads to rapid serotonin release well in advance of melatonin production, the question arises as to the physiological significance of serotonin secretion. The present studies examined the impact of ketanserine, a specific serotonin type 2 receptor antagonist, on the cyclic AMP and melatonin response of cultured rat pinealocytes to adrenergic stimuli. Whereas the beta-adrenergic agonist isoproterenol (1 microM) stimulated cAMP accumulation as well as melatonin release significantly, the presence of ketanserine inhibited these responses in a dose dependent manner. Since the same inhibitory effect of ketanserine was seen in cells stimulated by dibutyryl-cAMP (which acts post-adrenergic receptor to elevate melatonin synthesis), the mechanism for serotonin's feedback actions does not appear to involve changes in adrenergic receptor/cAMP coupling. These results indicate that extracellular serotonin may be important for the full activation of melatonin secretion following adrenergic stimulation.