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Melatonin receptor potentiation of cyclic AMP and the cystic fibrosis transmembrane conductance regulator ion channel
Author(s) -
Nelson Cole S.,
Marino Jennifer L.,
Allen Charles N.
Publication year - 1999
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.1999.tb00571.x
Subject(s) - melatonin , melatonin receptor , medicine , endocrinology , cystic fibrosis transmembrane conductance regulator , adenylyl cyclase , receptor , biology , forskolin , long term potentiation , stimulation , chemistry , cystic fibrosis
We have used the cystic fibrosis transmembrane conductance regulator (CFTR) CI‐ channel as a model system to study the cAMP signal transduction pathways coupled to the Xenopus melatonin receptor. During forskolin (Fsk) stimulation, melatonin reduced the amplitude of the CFTR currents in oocytes injected with in vitro transcribed cRNAs for the Xenopus melatonin receptor and CFTR. Pertussis toxin (Ptx) treatment eliminated melatonin inhibition of Fsk stimulated CFTR currents. In oocytes injected with cRNA for melatonin receptors, serotonin receptors (5‐HT 7 ). and CFTR CI − channels, application of melatonin together with serotonin (5‐HT) activated an additional inward current showing potentiation of adenylyl cyclases by melatonin receptors. Subthreshold activation of 5‐HT 7 receptors was sufficient and necessary to permit activation of CFTR channels by melatonin. Preexposure to melatonin desensitized 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 adenylyl cyclase stimulation.