Extracellular ATP and cAMP as Paracrine and Interorgan Regulators of Renal Function P2Y Receptors of MDCK Cells: Epithelial Cell Regulation by Extracellular Nucleotides

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Abstract
SUMMARY: 1. Madin–Darby canine kidney (MDCK) cells, a well‐ differentiated renal epithelial cell line derived from distal tubule/collecting duct, respond to extracellular nucleotides by altering ion flux and the production of arachidonic acid‐derived products, in particular prostaglandin E2 (PGE2). Our work has defined the receptors and signalling events involved in such responses.2. We have found evidence for expression of at least three P2Y receptor subtypes (P2Y1, P2Y2 and P2Y11) in MDCK‐D1 cells, a subclone from parental MDCK.3. These receptors appear to couple to increases in calcium and protein kinase C activity, probably via a Gq/G11‐mediated activation of phospholipase C.4. In addition, P2Y receptor activation can promote a prominent increase in cAMP. This includes both a P2Y2 receptor‐mediated cyclo‐oxygenase (COX)‐dependent component and another COX‐independent component mediated by other P2Y receptors.5. We have documented that changing media in which cells are grown releases ATP and, in turn, activates P2Y receptors. Such release of ATP contributes in a major way to basal cAMP levels in these cells.6. The data indicate that MDCK cells are a useful model to define the regulation of epithelial cells by extracellular nucleotides. Of particular note, spontaneous or stretch‐induced release of ATP and subsequent activation of one or more P2Y receptors contributes to establishing the basal activity of signalling pathways.