S1R agonist modulates rat platelet eicosanoid synthesis and aggregation

Abstract

Sigma-1 receptor (S1R) is detected in different cell types and can regulate intracellular signaling pathways. S1R plays a role in the pathomechanism of diseases and the regulation of neurotransmitters. Fluvoxamine can bind to S1R and reduce the serotonin uptake of neurons and platelets. We therefore hypothesized that platelets express S1R, which can modify platelet function. The expression of the SIGMAR1 gene in rat platelets was examined with a reverse transcription polymerase chain reaction and a quantitative polymerase chain reaction. The receptor was also visualized by immunostaining and confocal laser scanning microscopy. The effect of S1R agonist PRE-084 on the eicosanoid synthesis of isolated rat platelets and ADP- and AA-induced platelet aggregation was examined. S1R was detected in rat platelets both at gene and protein levels. Pretreatment with PRE-084 of resting platelets induced elevation of eicosanoid synthesis. The rate of elevation in thromboxane B₂ and prostaglandin D₂ synthesis was similar, but the production of prostaglandin E₂ was higher. The concentration-response curve showed a sigmoidal form. The most effective concentration of the agonist was 2 µM. PRE-084 increased the quantity of cyclooxygenase-1 as detected by ELISA. PRE-084 also elevated the ADP- and AA-induced platelet aggregation. S1R of platelets might regulate physiological or pathological functions.

Keywords:

• Aggregation
• eicosanoid
• platelets
• PRE-084
• Sigma-1 receptor

Acknowledgements

We wish to thank Anita Kiss and Anikó Váradi, at the Institute of Laboratory Medicine for their technical assistance with aggregometry.

Disclosure statement

The authors declare no conflict of interest.

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Additional information

Funding

This study was funded by the National Research, Development and Innovation Office of Hungary, grant number GINOP-2.3.2-15-2016-00060, by the EU-funded Hungarian grant EFOP-3.6.2-16-2017-00006, and by the Gedeon Richter Talentum Foundation (1103 Budapest, Gyömrői út 19-21.). M.M. was supported by the National Talent Programme with financial aid from the Ministry of Human Capacities (NTP-NFTÖ-20-B-0375). We wish to thank Dr. József Mihály (Biological Research Centre) for providing the α-tubulin antibody. S.V. was supported by the Premium Postdoctoral Research Programme (Premium-2019-469.