Chapter 43: Overview of the PAR-2 Receptor

INTRODUCTION

Protease-activated receptor-2 (PAR-2) is a G-protein-coupled receptor that is able to enhance the capacity of keratinocytes to ingest melanosomes from the neighboring melanocyte. Each melanocyte is in contact with an average of 36 keratinocytes forming an “epidermal melanin unit” (Figure 43-1).^1,2 Once melanin is created within melanosomes, it migrates into the dendrite tips of the melanocyte and is then incorporated into other keratinocytes of the epidermal melanin unit. Although the exact process of melanin transfer is not completely understood, PAR-2 has been shown to play an important role.³ The PAR-2 can be up- or downregulated, and is upregulated by ultraviolet radiation.⁴ It is thought to be important in hyperpigmentation disorders because it has been found that serine protease inhibitors that interfere with PAR-2 activation induce depigmentation by reducing melanosome transfer and distribution.⁵ Soybeans, which contain the serine protease inhibitors soybean trypsin inhibitor (STI) and Bowman–Birk protease inhibitor (BBI), have been demonstrated to inhibit melanosome transfer, resulting in an improvement of mottled facial pigmentation.⁶ In addition, activation of PAR-2 with trypsin and other synthetic peptides has been shown to result in visible skin darkening.⁵

Other systems play a role in melanosome transfer as well. For example, β-amyloid precursor protein (APP) is a newly detected epidermal growth factor that has been demonstrated to increase the release of melanin as well as enhance the movements of the melanocyte dendritic tips.⁷ Keratinocyte growth factor also promotes melanosome transfer by stimulating the phagocytic process.⁸ Many different factors affect melanosome transfer and play a role in the complex pigmentation process. At this time, only PAR-2 blockers have been added in cosmeceutical skin care products to block the transfer of melanosomes, so this section will focus on these agents. PAR-2 blockers do not break down melanin that is already in keratinocytes; therefore, results will not be seen for 8 to 16 weeks of using such skin care products.

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