@article{APS8278,
author = {Sheikh Arshad SAEED and Huma RASHEED and Faisal A Wahed RECTO and Mohammad Ilyas ACHAKZAI and Rahmat ALI and John Dennis CONNOR and Anwar-ul-Hassan GILANI},
title = {Signaling mechanisms mediated by G-protein coupled receptors in human platelets},
journal = {Acta Pharmacologica Sinica},
volume = {25},
number = {7},
year = {2016},
keywords = {},
abstract = {AIM:
The present study deals with the investigation of mechanisms involved in the synergistic interaction between epinephrine and arachidonic acid (AA).
METHODS:
Venous blood was taken from healthy human volunteers reported to be free of medications for one week. Platelet aggregation was monitored at 37 degree using Dual-channel Lumi-aggregometer. The resulting aggregation was recorded for 5 min by the measurement of light transmission as a function of time.
RESULTS:
The data show that a synergism in platelet aggregation mediated by subthreshold concentrations of epinephrine (1 micromol/L) and AA (0.2 micromol/L) was inhibited by the alpha2-receptor antagonist (yohimbine, IC50)=0.6 micromol/L) and an inhibitor of AA-cyclooxygenase (COX), indomethacin (IC50=0.25 micromol/L). In examining receptor influence on intraplatelet signalling pathways, it was found that the synergistic effect was inhibited by calcium channel blockers, verapamil (IC50=0.4 micromol/L) and diltiazem (IC50=2.5 micromol/L), as well as by low concentrations of inhibitors of phospholipase C (PLC) (U73122; IC50=0.2 micromol/L) and mitogens activated protein kinase (MAPK) (PD 98059; IC50=3.8 micromol/L). Herbimycin A, a specific inhibitor of tyrosine light chain kinase (TLCK), showed inhibition at IC50 value of 15 micromol/L, whereas chelerythrine, a protein kinase C (PKC) inhibitor, had no effect up to 20 micromol/L.
CONCLUSION:
These data suggest that synergism between epinephrine and AA in platelet aggregation is triggered through receptors coupled to G-protein, which in turn, activate PLC, COX, and MAP kinase-signaling pathways.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/8278}
}