Melatonin receptor potentiation of cyclic AMP and the cystic fibrosis transmembrane conductance regulator ion channel

We have used the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel as a model system to study the cAMP signal transduction pathwa ys coupled to the Xenopus melatonin receptor. During forskolin (Fsk) stimul ation, melatonin reduced the amplitude of the CFTR currents in oocytes inje cted with in vitro transcribed cRNAs for the Xenopus melatonin receptor and CFTR. Pertussis toxin (Ptx) treatment eliminated melatonin inhibition of F sk stimulated CFTR currents. In oocytes injected with cRNA for melatonin re ceptors, serotonin receptors (5-HT7), and CFTR Cl- channels, application of melatonin together with serotonin (5-HT) activated an additional inward cu rrent showing potentiation of adenylyl cyclases by melatonin receptors. Sub threshold activation of 5-HT7 receptors was sufficient and necessary to per mit activation of CFTR channels by melatonin. Preexposure to melatonin dese nsitized the melatonin receptor mediated response. Therefore, based on this model system, the effects of melatonin in vivo could be either positive or negative modulation of other neuronal inputs, depending on the mode of ade nylyl cyclase stimulation.