Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes

Abstract

Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis.

A Rose Extract Protects the Skin against Stress Mediators: A Potential Role of Olfactory Receptors

“…The current study showed that OR10A6, OR2AG2, and OR11H4 RNA transcripts and proteins are expressed both in vitro in keratinocytes and ex vivo in skin biopsies. These findings are not surprising since other ORs have already been described in skin cells, such as OR2AT4, OR6M1, OR5V1, OR11A1, OR6V1 [ 16 ], OR2A4/7, and OR51B5 in keratinocytes [ 17 ], or OR2A4/7 and OR51E2 in melanocytes [ 18 , 19 ]. Interestingly, we noticed that the expression patterns of the three ORs differ between skin explants and epidermis.…”

“…Previous OR studies in keratinocytes have demonstrated that OR agonists can activate the cAMP intracellular pathway [ 18 , 19 ]. Accordingly, within 30 min of application, the rose extract increased cAMP levels in NHEK ( Figure 2 ).…”

“…Since the 1990′s, the expression of human ORs has been found in various human normal and diseased tissues [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Previous studies have reported the existence and the role of such receptors in keratinocytes [ 16 ] and melanocytes [ 18 , 19 ]. Here, we investigated the presence of new skin ORs and the discovery of agonists to address the question of a potential involvement of these receptors in the handling of chronic skin stress.…”

“…For its part, OR51B5 seems to promote wound healing by supporting both keratinocyte migration and inflammatory processes, with secretion of cytokines, when stimulated with agonists such as the isononyl alcohol or the cyclohexyl salicylate [ 17 ]. Moreover, melanocytes present in the basal layer of the skin epidermis express OR51E2 [ 18 ] and OR2A4/7 [ 19 ]. A role in the biosynthesis of melanin is suspected for these two receptors through increased levels of intracellular cAMP and Ca 2+ following their activation by odorant ligands [ 19 ].…”

“…Moreover, melanocytes present in the basal layer of the skin epidermis express OR51E2 [ 18 ] and OR2A4/7 [ 19 ]. A role in the biosynthesis of melanin is suspected for these two receptors through increased levels of intracellular cAMP and Ca 2+ following their activation by odorant ligands [ 19 ]. Being directly exposed to the environment, the skin is highly susceptible to environmental stressors.…”