Human Platelets Express Functional α7-Nicotinic Acetylcholine Receptors

Abstract

Objective-Nicotinic acetylcholine receptors, especially ␣7 (nAChR␣7), form Ca 2ϩ 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 nAChR␣7 subunits, as revealed by mRNA and protein expression. The subunits form functional Ca 2ϩ channels, as demonstrated by Ca 2ϩ entry in platelets induced by the nAChR␣7-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 nAChR␣7-selective antagonists ␣-bungarotoxin and methyllycaconitine. Conclusion-Ca2ϩ influx via nAChR␣7 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 nAChR␣7 channels and thereby contributes to maintaining intracellular Ca

Expression and Functional Role of α7 Nicotinic Receptor in Human Cytokine-stimulated Natural Killer (NK) Cells

“…PNU-282987 causes a sustained increase in [Ca 2ϩ ] i in human NK cells, which is larger in the presence of a PAM. Similar types of responses were reported in other human non-neuronal cells, such as mesenchymal stem cells (43), endothelial cells (44), peripheral blood lymphocytes and leukemic cell lines (31,45), and platelets (46). The relatively slow response may be due to the fact that the release of Ca 2ϩ from intracellular stores is the underlying mechanism associated to ␣7 nAChR activation in these cells.…”

The Inflammatory Reflex and Neural Tourniquet: Harnessing the Healing Power of the Vagus Nerve

“…Based again on the Inflammatory Reflex, the most logical candidate is the α7 nicotinic acetylcholine receptor subunit (7nAChR). Interestingly, a previous study identified expression of α7nAChR mRNA and protein on human platelets [49]. α7nAChR forms functional calcium channels and allow for calcium entry into cells.…”

N‐methyl‐d‐aspartate receptor mediated calcium influx supports in vitro differentiation of normal mouse megakaryocytes but proliferation of leukemic cell lines

“…However, megakaryocytes also express other Ca 2+ channels, including transient receptor potential cation (TRPC),25 P2X,26 P2Y,27, 28 nicotinic cholinergic29 and N ‐methyl‐ d ‐aspartate (NMDA) receptors (NMDARs) 30, 31. NMDARs are non‐specific cation channels with high Ca 2+ permeability activated by extracellular glutamate 32.…”