title: Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation.
abstract: 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. Agonist-induced granular secretions of serotonin and concomitant P-selectin expression were also augmented by salsolinol. alpha2-adrenergic blockers attenuated the salsolinol-enhanced aggregation and the inhibition of cyclic AMP generation was found, suggesting the involvement of alpha2-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 alpha2-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.
authors.affiliation: College of Pharmacy, Seoul National University, Shinrim-dong San 56-1, Seoul 151-742, Korea.
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: Ji-Yoon
authors.initials: JY
authors.lastname: Noh
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Chung
authors.forename: Keunyoung
authors.initials: K
authors.lastname: Kim
authors.forename: Suyoung
authors.initials: S
authors.lastname: Hong
authors.forename: Sue
authors.initials: S
authors.lastname: Shin
authors.forename: Jong-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Chung
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival; D002712:Chlorides; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D009498:Neurotoxins / Q000378:metabolism* / Q000633:toxicity; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
chemical_list: D018674:Adrenergic Antagonists; D002712:Chlorides; D005290:Ferric Compounds; D007546:Isoquinolines; D009498:Neurotoxins; D019007:P-Selectin; D018341:Receptors, Adrenergic, alpha-2; D012701:Serotonin; C036617:salsolinol; D000242:Cyclic AMP; C024555:ferric chloride