Regulation of epidermal homeostasis through P2Y2 receptors

1 Previous studies have indicated a role for extracellular ATP in the regulation of epidermal homeostasis. Here we have investigated the expression of P2Y(2) receptors by human keratinocytes, the cells which comprise the epidermis. 2 Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of mRNA for the G-protein-coupled, P2Y(2) receptor in primary cultured human keratinocytes. 3 In situ hybridization studies of skin sections revealed that P2Y(2) receptor transcripts were expressed in the native tissue. These studies demonstrated a striking pattern of localization of P2Y(2) receptor transcripts to the basal layer of the epidermis, the site of cell proliferation. 4 Increases in intracellular free Ca2+ concentration ([Ca2+](i)) in keratinocytes stimulated with ATP or UTP demonstrated the presence of functional P2Y receptors. 5 In proliferation studies based on the incorporation of bromodeoxyuridine (BrdU), ATP, UTP and ATP gamma S were found to stimulate the proliferation of keratinocytes. 6 Using a real-time firefly luciferase and luciferin assay we have shown that under static conditions cultured human keratinocytes release ATP. 7 These findings indicate that P2Y(2) receptors play a major role in epidermal homeostasis, and may provide novel targets for therapy of proliferative disorders of the epidermis, including psoriasis.