Inhibition of basal and ultraviolet B-induced melanogenesis by cannabinoid CB(1) receptors: a keratinocyte-dependent effect.

Abstract

Ultraviolet radiation is the major environmental insult to the skin and stimulates the synthesis of melanin in melanocytes, which then distribute it to the neighboring keratinocytes where it confers photo-protection. Skin color results from the paracrine interaction between these two cell types. Recent studies suggest that endocannabinoids are potential mediators in the skin. Here, we investigated whether cannabinoid drugs play a role in melanogenesis and if ultraviolet radiation modifies the cutaneous endocannabinoid system. We used human melanotic melanoma cell line (SK-mel-1) in monoculture or co-culture with human keratinocytes (HaCat). Endocannabinoid levels, cannabinoid receptors expression, and melanin content were evaluated under basal conditions and after ultraviolet-B irradiation (311 nm). We provide evidence that human melanoma cells (SK-mel-1) express CB(1) receptors, and when in co-culture with keratinocytes (HaCat), the selective CB(1) receptor agonist arachidonyl-2-chloroethylamide (ACEA 1 and 10 μM) inhibited (by 33.4 and 37.3%, respectively) basal melanogenesis. In addition, ultraviolet-B-induced melanogenesis in co-cultures was abolished by ACEA 10 μM. Both ACEA inhibitory effects were reversed by AM251 (1 μM), a selective CB(1) antagonist. Furthermore, ultraviolet-B radiation increased endocannabinoids levels only in keratinocytes, whereas CB(1) cannabinoid receptor expression was up-regulated only in melanoma cells. Our results collectively suggest that ultraviolet radiation activates paracrine CB(1)-mediated endocannabinoid signaling to negatively regulate melanin synthesis. The endocannabinoid system in the skin may be a possible target for future therapies in pigmentary disorders.

• Authors: Sofia Magina, Carina Esteves-Pinto, Eduardo Moura, Maria Paula Serrão, Daniel Moura, Stefania Petrosino, Vincenzo Di Marzo, Maria Augusta Vieira-Coelho
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 303 Issue 3 Pg. 201-10 (Apr 2011) ISSN: 1432-069X [Electronic] Germany
• PMID: 21298280 (Publication Type: Journal Article)

Chemical References

• Arachidonic Acids
• Cannabinoid Receptor Modulators
• Melanins
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• arachidonyl-2-chloroethylamide
• AM 251

Topics

• Arachidonic Acids (pharmacology)
• Cannabinoid Receptor Modulators (metabolism)
• Cell Line, Tumor
• Coculture Techniques
• Down-Regulation (drug effects)
• Humans
• Keratinocytes (drug effects, metabolism, pathology, radiation effects)
• Melanins (genetics, metabolism)
• Melanocytes (drug effects, metabolism, pathology, radiation effects)
• Paracrine Communication
• Pigmentation Disorders (drug therapy)
• Piperidines (pharmacology)
• Pyrazoles (pharmacology)
• Receptor, Cannabinoid, CB1 (agonists, antagonists & inhibitors, genetics, metabolism)
• Skin (pathology)
• Ultraviolet Rays