Gene expression profiling for the identification of G-protein coupled receptors in human platelets
Amisten, Stefan LU ; Braun, Oscar LU ; Bengtsson, Anders LU and Erlinge, David LU
(2008)
In Thrombosis Research
122(1).
p.47-57
- Abstract
- 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%), ADP 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 EBI2 (6.31+/-0.42), adenosine receptors A(2A) (2.94+/-0.24%) and A(2B)... (More)
- 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%), ADP 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 EBI2 (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)). A surprising G-protein coupled receptor redundancy was found: two ADP receptors (P2Y(1) and P2Y(12)), three adenosine receptors (A(2A), A(2B), and A(1)), four lysophosphatidic acid receptors (LPA(1), LPA(3), GPR23 and GPR92), two l-glutamate receptors (mGlu(3) and mGlu(4)) and two serotonin receptors (5-HT(1F) and 5-HT(4)). The adenosine receptor A(2B) gene expression was validated with protein expression and functional studies. Western blot confirmed A(2B) 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1140022
- author
- Amisten, Stefan
LU
; Braun, Oscar
LU
; Bengtsson, Anders
LU
and Erlinge, David
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- GPCR, Adenosine, Microarray, P2 receptors, mRNA, Platelets
- in
- Thrombosis Research
- volume
- 122
- issue
- 1
- pages
- 47 - 57
- publisher
- Elsevier
- external identifiers
-
- pmid:17920662
- wos:000256114100007
- scopus:42649146229
- ISSN
- 1879-2472
- DOI
- 10.1016/j.thromres.2007.08.014
- language
- English
- LU publication?
- yes
- id
- bf0876cb-d861-449e-8af4-8caa154a1a0b (old id 1140022)
- date added to LUP
- 2016-04-01 11:57:22
- date last changed
- 2022-04-28 22:28:32
@article{bf0876cb-d861-449e-8af4-8caa154a1a0b,
abstract = {{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%), ADP 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 EBI2 (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)). A surprising G-protein coupled receptor redundancy was found: two ADP receptors (P2Y(1) and P2Y(12)), three adenosine receptors (A(2A), A(2B), and A(1)), four lysophosphatidic acid receptors (LPA(1), LPA(3), GPR23 and GPR92), two l-glutamate receptors (mGlu(3) and mGlu(4)) and two serotonin receptors (5-HT(1F) and 5-HT(4)). The adenosine receptor A(2B) gene expression was validated with protein expression and functional studies. Western blot confirmed A(2B) 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.}},
author = {{Amisten, Stefan and Braun, Oscar and Bengtsson, Anders and Erlinge, David}},
issn = {{1879-2472}},
keywords = {{GPCR; Adenosine; Microarray; P2 receptors; mRNA; Platelets}},
language = {{eng}},
number = {{1}},
pages = {{47--57}},
publisher = {{Elsevier}},
series = {{Thrombosis Research}},
title = {{Gene expression profiling for the identification of G-protein coupled receptors in human platelets}},
url = {{http://dx.doi.org/10.1016/j.thromres.2007.08.014}},
doi = {{10.1016/j.thromres.2007.08.014}},
volume = {{122}},
year = {{2008}},
}