Endocannabinoids stimulate human melanogenesis via type-1 cannabinoid receptor

Mariangela Pucci, Nicoletta Pasquariello, Natalia Battista, Monia Di Tommaso, Cinzia Rapino, Filomena Fezza, Michela Zuccolo, Roland Jourdain, Alessandro Finazzi Agrò, Lionel Breton, Mauro Maccarrone

Research output: Contribution to journalArticlepeer-review


We show that a fully functional endocannabinoid system is present in primary human melanocytes (normal human epidermal melanocyte cells), including anandamide (AEA), 2-arachidonoylglycerol, the respective target receptors (CB1, CB2, and TRPV1), and their metabolic enzymes. We also show that at higher concentrations AEA induces normal human epidermal melanocyte apoptosis (∼3-fold over controls at 5 μM) through a TRPV1-mediated pathway that increases DNA fragmentation and p53 expression. However, at lower concentrations, AEA and other CB1-binding endocannabinoids dose-dependently stimulate melanin synthesis and enhance tyrosinase gene expression and activity (∼3- and ∼2-fold over controls at 1 μM). This CB1-dependent activity was fully abolished by the selective CB1antagonist SR141716 or by RNA interference of the receptor. CB1 signaling engaged p38 and p42/44 mitogen-activated protein kinases, which in turn activated the cyclic AMP response element-binding protein and the microphthalmia-associated transcription factor. Silencing of tyrosinase or microphthalmiaassociated transcription factor further demonstrated the involvement of these proteins in AEA-induced melanogenesis. In addition, CB1 activation did not engage the key regulator of skin pigmentation, cyclic AMP, showing a major difference compared with the regulation of melanogenesis by α-melanocyte-stimulating hormone through melanocortin 1 receptor.

Original languageEnglish
Pages (from-to)15466-15478
Number of pages13
JournalJournal of Biological Chemistry
Issue number19
Publication statusPublished - May 4 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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