RESUMO
A3 adenosine receptor, A3AR, belongs to the Gi proteins coupled receptors. Activation of A3AR by its agonist, IB-MECA, decreases cAMP and was expected to reduce melanin level. Unexpectedly, B16 melanoma cells exposed to IB-MECA increased melanin levels in a dose-dependent manner. Human skin explants exposed to IB-MECA showed an increase in DOPA positive cells and in melanin deposition in keratinocytes. The agonist induced AKT phosphorylation, leading to a rapid translocation of the transcription factor MiTF towards the nucleus. DOPA oxidase activity and melanin levels induced by IB-MECA were further enhanced by PD98509, an inhibitor ERK signalling pathway. Our study shows that IB-MECA decreases cAMP while inducing melanogenesis. The proposed mechanism involves activation of PI3K/AKT signalling pathway by ß/γ subunits of the G protein coupled to A3AR. The increase in melanin level in human skin explants suggests that IB-MECA may be a potential candidate to the treatment of hypopigmentation of skin.
