Jl. Daniel et al., MOLECULAR-BASIS FOR ADP-INDUCED PLATELET ACTIVATION I - EVIDENCE FOR 3 DISTINCT ADP RECEPTORS ON HUMAN PLATELETS, The Journal of biological chemistry, 273(4), 1998, pp. 2024-2029
Acting through cell surface receptors, ADP activates platelets resulti
ng in shape change, aggregation, thromboxane A(2) production, and rele
ase of granule contents, ADP also causes a number of intracellular eve
nts including inhibition of adenylyl cyclase, mobilization of calcium
from intracellular stores, and rapid calcium influx in platelets, Howe
ver, the receptors that transduce these events remain unidentified and
their molecular mechanisms of action have not been elucidated. The re
ceptor responsible for the actions of ADP On platelets has been design
ated the P2T receptor, In this study we have used ARL 66096, a potent
antagonist of ADP-induced platelet aggregation, and a P2X ionotropic r
eceptor agonist, alpha,beta-methylene adenosine 5'-triphosphate, to di
stinguish the ADP-induced intracellular events, ARL 66096 blocked ADP-
induced inhibition of adenylyl cyclase, but did not affect ADP-mediate
d intracellular calcium increases or shape change, Both ADP and 2-meth
ylthio-ADP caused a 3-fold increase in the level of inositol 1,4,5-tri
sphosphate over control levels which peaked in a similar fashion to th
e Ca2+ transient. The increase in inositol 1,3,4-trisphosphate was of
similar magnitude to that of inositol 1,4,5-trisphosphate. alpha,beta-
Methylene adenosine 5'-triphosphate did not cause an increase in eithe
r of the inositol trisphosphates. These results clearly demonstrate th
e presence of two distinct platelet ADP receptors in addition to the P
2X receptor: one coupled to adenylyl cyclase and the other coupled to
mobilization of calcium from intracellular stores through inositol tri
sphosphates.