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Pharmacol Res. 2010 Dec;62(6):500-5. doi: 10.1016/j.phrs.2010.08.003. Epub 2010 Sep 8.

P2Y(13) receptor is responsible for ADP-mediated degranulation in RBL-2H3 rat mast cells.

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Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0810, USA.


Extracellular ADP is known to play many important physiological roles. In this study, we identified the P2Y(13) receptor in a rat mast cell line (RBL-2H3) and explored the functional role of ADP, its endogenous agonist. ADP induced both intracellular calcium mobilization and release of hexosaminidase (Hex). In an assay of intracellular calcium, ADP was 100-fold less potent than and equally efficacious as the P2Y(1) receptor-selective agonist MRS2365. However, ADP was more potent and efficacious than MRS2365 in inducing Hex release and in enhancing antigen-induced Hex release. ADP-induced intracellular calcium mobilization was blocked by phospholipase C inhibitor U73122 and by P2Y(1) receptor-selective antagonist MRS2500, but not by pertussis toxin (PTX), suggesting a mechanism mediated by the G(q)-coupled P2Y(1) receptor, but not P2Y(13) (G(i)-coupled) or P2X receptors. ADP-induced Hex release was blocked by PTX and a selective P2Y(13) receptor antagonist MRS2211, but not by MRS2500 or P2Y(1) receptor-specific siRNA, suggesting a G(i)-coupled P2Y(13) receptor-related mechanism. Measurement of gene expression confirmed high expression of both P2Y(1) and P2Y(13) receptors (in comparison to a previously reported P2Y(14) receptor) in RBL-2H3 cells. Thus, we demonstrated that ADP-mediated intracellular calcium mobilization and Hex release in RBL-2H3 cells are via P2Y(1) and P2Y(13) receptors, respectively. Selective antagonists of the P2Y(13) receptor might be novel therapeutic agents for various allergic conditions.

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