Possible Interaction: Melatonin and Colforsin

“The inhibitory effects of melatonin were reversible and preventable with either melatonin receptor antagonist S20928, pertussis toxin, forskolin , or 8‐Br‐cAMP.”

“Acute melatonin treatment (6 h) in the presence of either forskolin or 3-isobutyl-1-methylxanthine caused a significant decrease in insulin release and induced significant downregulation of calcium/calmodulin-dependent kinase IV and calcium/calmodulin-dependent kinase 2d transcripts in INS-1 batch cultures.”

“Pretreatment of either MT(1)- or MT(2)-CHO cells with melatonin (1 microM for 5hr) resulted in: (a) a complete loss of melatonin-mediated stimulation of PI hydrolysis, and (b) an attenuation of melatonin (1nM)-mediated inhibition of forskolin-induced cAMP accumulation by approximately 20-40%.”

“ Forskolin , an adenylate cyclase activator, prevented the protective effects of melatonin ; inhibitors of protein kinase C and mitogen‐associated protein kinase had no detectable effect.”

“This inhibitory effect of melatonin is reversible with either pertussis toxin, forskolin or cAMP.”

“In Chinese hamster ovary cells expressing human mt1 or MT2 receptors, both melatonin and GR196429 dose-dependently inhibited forskolin-stimulated cAMP accumulation.”

“ Melatonin (1 microM) decreased the forskolin (10 microM) stimulated cAMP level by 50%.”

“Cells pretreated with melatonin revealed a persistent inhibition (approximately 20%) of forskolin-induced cAMP formation that was not reversed by extensive washes (up to 1 hr) or when luzindole (1 microM) was added together with melatonin during pretreatment.”

“Low concentrations of melatonin (0.01 fM-1 PM) inhibited forskolin (100 microM)-stimulated cAMP formation with an IC50 of 0.1 +/- 0.05 PM (four experiments) and a maximal inhibitory effect (26%) at 1 PM.”

“ Melatonin (0.1 fM-1 nM) inhibited forskolin-induced cAMP formation in a concentration-dependent and biphasic manner.”

“… melatonin (1 … forskolin-induced cAMP formation with an IC50 of 64 +/- 1.8 PM (four experiments) and a maximal inhibition (74%) at 1 nM. Luzindole (1 microM), … antagonist, antagonized the effect of melatonin at the higher concentrations only (IC50 = 1.5 +/- 0.22 nM, pKB = -7.3; three experiments).”

“ Melatonin (10 nm) was consistently found to be a highly potent inhibitor of the activation of MAPK induced by forskolin ; in contrast, melatonin did not inhibit the activation of MAPK induced by IGF-1.(ABSTRACT TRUNCATED AT 400 WORDS)”

“ Melatonin and iodomelatonin caused dose-dependent reductions in forskolin-stimulated cAMP production with half-maximal values of 2.4 x 10(-9)M and 3.28 x 10(-9)M, respectively.”