Human platelets express functional alpha7-nicotinic acetylcholine receptors.
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.


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.
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
Angelika
A
Schedel
Sophia
S
Thornton
Patrick
P
Schloss
Harald
H
Klüter
Peter
P
Bugert
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D012333:RNA, Messenger / Q000097:blood; D039341:Receptors, Fibrinogen / Q000097:blood; D011978:Receptors, Nicotinic / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D002038:Bungarotoxins; C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; C498513:PNU-282987; D012333:RNA, Messenger; D039341:Receptors, Fibrinogen; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D002118:Calcium; D000157:Aconitine