Key result
Coexisting P2u and P2y receptors on MDCK-D1 cells promote arachidonic acid release via activation of phospholipase A2, with distinct signaling pathways and desensitization patterns.
Demonstrates for the first time that P2u and P2y purinergic receptors coexist on renal epithelium cells and promote arachidonic acid release, likely via phospholipase A2 activation.
No immediate clinical implications from canine cell data; leaves open in vivo relevance to human renal purinergic signaling.
We have characterized the signaling pathways of purinergic receptors present on the renal epithelial cell line, Madin-Darby canine kidney (MDCK, D1 subclone). Several lines of evidence are consistent with the conclusion that coexisting P2u and P2y receptors release arachidonic acid and metabolites (AA) from MDCK-D1 cells: 1) relative potencies of nucleotide analogues, 2) blockade of P2y agonist- but not P2u agonist-mediated release by suramin, and 3) additivity by 2-methylthio-ATP and UTP. Differences exist between the signaling pathways of the two receptors: pertussis toxin treatment partially inhibits P2u- but not P2y-mediated AA release, and P2y (but not P2u) receptors appear to stimulate D-myo-inositol 1,4,5-trisphosphate production. P2u-receptor occupancy results in both homologous and heterologous desensitization; P2y-receptor occupancy elicits only homologous desensitization. Both receptors stimulate phosphatidylcholine hydrolysis via phospholipase C activation. However, AA release appears to result from phospholipid deacylation by phospholipase A2 activation, rather than from alternate pathways that may include PLC activation. These results demonstrate for the first time that two subtypes of P2-purinergic receptors, P2u and P2y receptors, coexist on a single renal epithelium cell type and that these two receptor subtypes can promote AA release, probably via activation of PLA2.
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Firestein et al. (1996) studied Renal epithelial cell line (MDCK, D1 subclone). P2u and P2y receptor agonists was evaluated on Arachidonic acid release and signaling pathways. Coexisting P2u and P2y receptors on MDCK-D1 cells promote arachidonic acid release via activation of phospholipase A2, with distinct signaling pathways and desensitization patterns.
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