P2Y13 receptor is responsible for ADP-mediated degranulation in RBL-2H3 rat mast cells

被引：38
作者：
Gao, Zhan-Guo [1 ]
Ding, Yi [2 ]
Jacobson, Kenneth A. [1 ]
机构：
[1] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA
[2] NIH, Ctr Clin, Bethesda, MD 20892 USA
来源：
PHARMACOLOGICAL RESEARCH | 2010年 / 62卷 / 06期
基金：
美国国家卫生研究院;
关键词：
P2Y13; receptor; Nucleotide; Mast cell; Degranulation; Allergy; G protein-coupled receptor; NUCLEOTIDE RECEPTORS; ACTIVATION; RELEASE; ANTAGONIST; EXPRESSION; HISTAMINE; PATHWAYS; AGONIST;
D O I：
10.1016/j.phrs.2010.08.003
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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(1)-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(1)-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 Published by Elsevier Ltd
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收藏
页码：500 / 505
页数：6
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