1. ^*Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, West Yorkshire, UK
2. ^†Institute for Pigmentary Disorders in Association with the Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany and University of Bradford, UK

Correspondence: Professor K. U. Schallreuter, Clinical and Experimental Dermatology, Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK. Email: k.schallreuter@bradford.ac.uk

Received 13 October 2003; Revised 3 March 2004; Accepted 15 March 2004.

Abstract

Earlier it has been shown that human proliferating/undifferentiated basal keratinocytes hold the full capacity for autocrine catecholamine synthesis/degradation and express ₂-adrenoceptors (₂-AR). In this report, we show that human melanocytes also express all of the mRNA and enzymes for autocrine synthesis of norepinephrine but fail to produce epinephrine. So far, it was established that human melanocytes express ₁-AR which are induced by norepinephrine yielding the inosine triphosphate diacylglycerol signal. The presence of catecholamine synthesis and the ₂-AR signal escaped definition at that time. Using RT-PCR, immunofluorescence and radioligand binding with the ₂-AR antagonist (-)-[³H]CGP 12177, we show here that human melanocytes express functional ₂-AR (4230 receptors per cell) with a B_max at 129.3 and a K_D of 3.19 nM but lack ₁-AR expression. ₂-AR stimulation with epinephrine 10^-6 M and salbutamol 10^-6–10^-5 M yielded a strong cyclic adenosine monophospate (cAMP) response in association with upregulated melanin production. Taken together these results indicate that the biosynthesis and release of epinephrine (10^-6 M) by surrounding keratinocytes can provide the cAMP response leading to melanogenesis in melanocytes via the ₂-AR signal. Moreover, the discovery of this catecholaminergic cAMP response in melanocytes adds a new source for this important second messenger in melanogenesis.