Schedel_2011_Arterioscler.Thromb.Vasc.Biol_31_928

OBJECTIVE: Nicotinic acetylcholine receptors, especially alpha7 (nAChRalpha7), form Ca(2+) channels and are expressed on a variety of neuronal and nonneuronal cells. Also, megakaryocytic cells have been shown to contain components of a nonneuronal cholinergic system, including acetylcholine and acetylcholine esterase. However, the corresponding nAChRs and their role in platelet function have not been demonstrated until now. Our previous platelet transcriptome data indicated the presence of nAChR gene transcripts. METHODS AND
RESULTS: Here, we present evidence that human platelets and megakaryocytic precursor cells express nAChRalpha7 subunits, as revealed by mRNA and protein expression. The subunits form functional Ca(2+) channels, as demonstrated by Ca(2+) entry in platelets induced by the nAChRalpha7-selective agonist PNU-282987. PNU-282987 also enhanced fibrinogen receptor activation induced by classical platelet agonists (the thromboxane A(2) analog U46619 and ADP). Furthermore, agonist-induced platelet aggregation was significantly inhibited by the nAChRalpha7-selective antagonists alpha-bungarotoxin and methyllycaconitine.
CONCLUSIONS: Ca(2+) influx via nAChRalpha7 channels represents a novel pathway for human platelets with significant impact on platelet function. Because platelets were suggested to contain acetylcholine, we conclude that on activation, stored acetylcholine is released, which activates nAChRalpha7 channels and thereby contributes to maintaining intracellular Ca(2+) levels and supporting platelet activation.