期刊
THROMBOSIS RESEARCH
卷 122, 期 1, 页码 47-57出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2007.08.014
关键词
platelets; mRNA; P2 receptors; microarray; adenosine; GPCR
Introduction and materials and methods: G-protein coupled receptors (GPCRs) play an important role in platelet aggregation. To identify new platelet GPCRs, a platelet gene expression profile was generated and validated using quantitative real-time PCR. Results: In total, mRNA of 28 GPCR genes was detected in human platelets. The 12 most abundant platelet GPCR transcripts were: thrombin receptor PAR1 (1865 +/- 178%), ADIP receptor P2Y(12) (459 +/- 88%), succinate receptor 1 (257 +/- 48%), ADP receptor P2Y(1) (100%), orphan P2RY(10) (68.2 +/- 3.3%), lysophosphatidic acid receptors GPR23 (48.2 +/- 11%) and GPR92 (26.1 +/- 3.3%), adrenergic receptor alpha(2A) (18.4 +/- 4.4%), orphan EB12 (6.31 +/- 0.42), adenosine receptors A(2A) (2.94 +/- 0.24%) and A(2B) (2.88 +/- 0.16%) and lysophosphatidic acid receptor LPA(1) (2.59 +/- 0.39%) (% relative to the chosen calibrator P2Y(1)). The adenosine receptor A(2B) gene expression was validated with protein expression and functional studies. Western blot confirmed A2B receptor protein expression and platelet flow cytometry demonstrated inhibition of the effect of NECA by the adenosine A(2B)-antagonist MRS1754. Conclusions: We have detected several GPCRs not previously known to be expressed in platelets, including a functional adenosine A(2B) receptor. The findings could improve our understanding of platelet aggregation and provide new targets for drug development. (C) 2007 Elsevier Ltd. All rights reserved.
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