Autocrine Catecholamine Biosynthesis and the β2-Adrenoceptor Signal Promote Pigmentation in Human Epidermal Melanocytes

Earlier it has been shown that human proliferating/undifferentiated basal keratinocytes hold the full capacity for autocrine catecholamine synthesis/degradation and express β2-adrenoceptors (β2-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 α1-AR which are induced by norepinephrine yielding the inosine triphosphate diacylglycerol signal. The presence of catecholamine synthesis and the β2-AR signal escaped definition at that time. Using RT-PCR, immunofluorescence and radioligand binding with the β2-AR antagonist (-)-[3H]CGP 12177, we show here that human melanocytes express functional β2-AR (4230 receptors per cell) with a Bmax at 129.3 and a KD of 3.19 nM but lack β1-AR expression. β2-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 β2-AR signal. Moreover, the discovery of this catecholaminergic cAMP response in melanocytes adds a new source for this important second messenger in melanogenesis