Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation
Ok-Nam Bae*1, Young-Dae Kim*1, Kyung-Min Lim1,2, Ji-Yoon Noh1, Seung-Min Chung1, Keunyoung Kim1, Suyoung Hong1, Sue Shin3, Jong-Hyun Yoon3, Jin-Ho Chung1
1College of Pharmacy, Seoul National University, Seoul, Korea; 2AMOREPACIFIC CO/R&D Center, Gyeonggi-do, Korea; 3Department of Laboratory Medicine, Boramae Hospital, Boramae, Korea
Parkinson’s disease, thrombosis, Alcoholism, Platelets, salsolinol
Salsolinol,an endogenous neurotoxin,is known to be involved in the neuropathy of Parkinson’s disease and chronic alcoholism. In these diseases, increased thrombotic events are also commonly reported, yet the mechanism underlying remains poorly understood. Here we report that salsolinol can enhance agonist-induced platelet aggregation and granular secretion, which is essential in the thrombus formation. In rat and human platelets, agonist-induced platelet aggregation was significantly increased by salsolinol in a concentration-dependent manner. Agonistinduced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. α2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of α2-adrenergic receptor-mediated pathways in these events. In accord with the in-vitro results, in an arterial and venous thrombosis model in vivo in the rat, salsolinol shortened vessel occlusion time and increased thrombus formation, respectively. In conclusion, we demonstrated that salsolinol can enhance agonist-induced aggregation and granular secretion in platelets through α2-adrenergic receptor activation, which resulted in the increased thrombus formation in vivo. These results suggest that salsolinol-enhanced platelet aggregation could be a possible contributing factor to the thrombotic events observed in Parkinson’s disease and alcoholism.