Title : Acetylcholine Inhibits Platelet Activation - Bennett_2019_J.Pharmacol.Exp.Ther_369_182 |
Author(s) : Bennett JA , Ture SK , Schmidt RA , Mastrangelo MA , Cameron SJ , Terry LE , Yule DI , Morrell CN , Lowenstein CJ |
Ref : Journal of Pharmacology & Experimental Therapeutics , 369 :182 , 2019 |
Abstract :
Platelets are key mediators of thrombosis. Many agonists of platelet activation are known, but fewer endogenous inhibitors of platelets, such as prostacyclin and nitric oxide (NO), have been identified. Acetylcholinesterase inhibitors, such as donepezil, can cause bleeding in patients, but the underlying mechanisms are not well understood. We hypothesized that acetylcholine is an endogenous inhibitor of platelets. We measured the effect of acetylcholine or analogs of acetylcholine on human platelet activation ex vivo. Acetylcholine and analogs of acetylcholine inhibited platelet activation, as measured by P-selectin translocation and glycoprotein IIb IIIa conformational changes. Conversely, we found that antagonists of the acetylcholine receptor, such as pancuronium, enhance platelet activation. Furthermore, drugs inhibiting acetylcholinesterase, such as donepezil, also inhibit platelet activation, suggesting that platelets release acetylcholine. We found that NO mediates acetylcholine inhibition of platelets. Our data suggest that acetylcholine is an endogenous inhibitor of platelet activation. The cholinergic system may be a novel target for antithrombotic therapies. |
PubMedSearch : Bennett_2019_J.Pharmacol.Exp.Ther_369_182 |
PubMedID: 30765424 |
Bennett JA, Ture SK, Schmidt RA, Mastrangelo MA, Cameron SJ, Terry LE, Yule DI, Morrell CN, Lowenstein CJ (2019)
Acetylcholine Inhibits Platelet Activation
Journal of Pharmacology & Experimental Therapeutics
369 :182
Bennett JA, Ture SK, Schmidt RA, Mastrangelo MA, Cameron SJ, Terry LE, Yule DI, Morrell CN, Lowenstein CJ (2019)
Journal of Pharmacology & Experimental Therapeutics
369 :182