Modulation by melatonin of protein secretion from melanoma cells: is cAMP involved?
The pineal hormone melatonin modulates constitutive protein secretion from melanoma M2R cells. Nanomolar concentrations of melatonin inhibited protein secretion early after plating or at low cell density, but facilitated it late after plating or at high cell density. Inhibition by melatonin of adenylate cyclase is the best known downstream response to melatonin. We have therefore examined the involvement of cAMP in the melatonin-mediated modulation of protein secretion from the melanoma cells. Melatonin slightly but significantly reduced cell cAMP content when effecting inhibition and marginally increased cAMP levels when effecting facilitation of protein secretion. Dibutyryl cAMP abrogated the melatonin-mediated inhibition but not facilitation of protein secretion without affecting basal secretion. Accordingly, forskolin prevented the inhibitory action of melatonin on protein secretion without affecting basal secretion. The selective protein kinase A inhibitor H-89 did not alter the inhibitory effect of melatonin at low cell density and slightly facilitated secretion at high cell density with or without melatonin. Thus, melatonin's effects on protein secretion may not be mediated via cAMP. Nevertheless, changes in cAMP or protein kinase A activity can abrogate, or mask, the melatonin-mediated responses.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D013449:Sulfonamides; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D011506:Proteins; D013449:Sulfonamides; D005576:Colforsin; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D008550:Melatonin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide