Platelets (Jul 2022)

S1R agonist modulates rat platelet eicosanoid synthesis and aggregation

  • Sándor Váczi,
  • L. Barna,
  • A. Harazin,
  • M. Mészáros,
  • G. Porkoláb,
  • Á. Zvara,
  • R. Ónody,
  • I. Földesi,
  • S. Veszelka,
  • B. Penke,
  • L. Fülöp,
  • M. A. Deli,
  • Z. Mezei

DOI
https://doi.org/10.1080/09537104.2021.1981843
Journal volume & issue
Vol. 33, no. 5
pp. 709 – 718

Abstract

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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.

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