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

Exp Dermatol. 2018 Nov;27(11):1216-1223. doi: 10.1111/exd.13764. Epub 2018 Sep 18.

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 Ca2+ 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.

Keywords: cAMP; MAPKs; calcium signalling; melanogenesis; olfactory receptor.

MeSH terms

  • Apoptosis / drug effects
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Membrane / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Humans
  • Ligands
  • Melanins / biosynthesis*
  • Melanocytes / physiology*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation / drug effects
  • Receptors, Odorant / metabolism*
  • Salicylates / chemistry
  • Salicylates / pharmacology
  • Signal Transduction

Substances

  • Ligands
  • Melanins
  • OR2A4 protein, human
  • OR2A7 protein, human
  • Receptors, Odorant
  • Salicylates
  • cyclohexyl salicylate
  • Cyclic AMP
  • Mitogen-Activated Protein Kinases
  • Calcium