P2Y12 receptor antagonists and AR receptor agonists regulates Protein Disulfide Isomerase secretion from platelets and endothelial cells

Abstract

Secretion of PDI from platelets and endothelial cells is an important step of all thrombotic events. In the absence of extracellular PDI thrombus formation and fibrin generation may be impaired. Thrombin-mediated PDI secretion is regulated by the stimulation of P2Y₁₂ receptors. This paper provides evidences that P2Y₁₂ antagonists or AR agonists may modulate release of PDI molecules from platelets and with less efficiency from endothelial cells. Moreover P2Y₁₂ antagonization or AR agonization modulates platelet-endothelial interaction. We prove that combinations of P2Y₁₂ antagonists and AR agonists inhibit platelet-dependent adhesion of cancer cells to endothelium and attenuate cancer cell invasiveness, but longer exposition to AR agonists may stimulate migration of invasive breast cancer cells through endothelium thus leading to increased metastasis.

Keywords: Adenosine receptor agonist; P2Y(12) antagonist; Protein disulfide isomerase; Thiol bonds.