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Thromb Haemost 2008; 100(01): 52-59
DOI: 10.1160/TH07-08-0529
Platelets and Blood Cells
Schattauer GmbH

Salsolinol, an endogenous neurotoxin, enhances platelet aggregation and thrombus formation

Ok-Nam Bae   *
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Young-Dae Kim   *
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Kyung-Min Lim
1   College of Pharmacy, Seoul National University, Seoul, Korea
2   AMOREPACIFIC CO/R&D Center, Gyeonggi-do, Korea
,
Ji-Yoon Noh
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Seung-Min Chung
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Keunyoung Kim
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Suyoung Hong
1   College of Pharmacy, Seoul National University, Seoul, Korea
,
Sue Shin
3   Department of Laboratory Medicine, Boramae Hospital, Boramae, Korea
,
Jong-HyunYo on
3   Department of Laboratory Medicine, Boramae Hospital, Boramae, Korea
,
Jin-Ho Chung
1   College of Pharmacy, Seoul National University, Seoul, Korea
› Author AffiliationsFinancial support: This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by MOST (RO1–2007–000–11252–0).
Further Information

Publication History

Received 29 August 2007

Accepted after major revision 06 May 2008

Publication Date:
22 November 2017 (online)

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Summary

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. 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 sal-solinol 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.

Keywords

Platelets - salsolinol - Parkinson’s disease - alcoholism - thrombosis

* These authors contributed equally to this work.


 

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