Angelika Schedel1, Sophia Thornton, Patrick Schloss, Harald Klüter, Peter Bugert. 1. Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service of Baden-Württemberg-Hessen, Friedrich-Ebert-Straße 107, D-68167 Mannheim, Germany. angelika.schedel@medma.uni-heidelberg.de
Abstract
OBJECTIVE: Nicotinic acetylcholine receptors, especially α7 (nAChRα7), 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 nAChRα7 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 nAChRα7-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 nAChRα7-selective antagonists α-bungarotoxin and methyllycaconitine. CONCLUSIONS: Ca(2+) influx via nAChRα7 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 nAChRα7 channels and thereby contributes to maintaining intracellular Ca(2+) levels and supporting platelet activation.
OBJECTIVE: Nicotinic acetylcholine receptors, especially α7 (nAChRα7), 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 nAChRα7 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 nAChRα7-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 nAChRα7-selective antagonists α-bungarotoxin and methyllycaconitine. CONCLUSIONS:Ca(2+) influx via nAChRα7 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 nAChRα7 channels and thereby contributes to maintaining intracellular Ca(2+) levels and supporting platelet activation.
Authors: John A Bennett; Sara K Ture; Rachel A Schmidt; Michael A Mastrangelo; Scott J Cameron; Lara E Terry; David I Yule; Craig N Morrell; Charles J Lowenstein Journal: J Pharmacol Exp Ther Date: 2019-02-14 Impact factor: 4.030
Authors: Tran Vu Thien; Hoang Ngoc Anh; Nguyen Thi Thuy Trang; Phung Van Trung; Nguyen Cuu Khoa; A V Osipov; P V Dubovskii; I A Ivanov; A S Arseniev; V I Tsetlin; Yu N Utkin Journal: Dokl Biochem Biophys Date: 2017-11-04 Impact factor: 0.788