Effects of Glycosaminoglycan from Urechis Unicinctus on the P2Y12 Receptor Signaling Pathway in Rat Platelets

This study aims to investigate the effects of glycosaminoglycan (GAG) from Urechis unicinctus on the P2Y12 receptor signaling pathway in rat platelets. The concentrations of cyclic adenosine monophosphate (cAMP), thromboxane B2 (TXB2) and glycoprotein IIb/IIIa (GPIIb/IIIa) in rat platelets were determined using enzyme-linked immunosorbent assay (ELISA) kits. The phosphorylation levels of protein kinase A (PKA) and vasodilator-stimulated phosphoprotein (VASP) in rat platelets were detected through Western blot. The expression of P2Y12 gene in rat platelets was analyzed via real-time fluorescence quantitative PCR and reverse-transcription PCR. It was observed that GAG significantly increased the cAMP content (plessthan 0.05, plessthan 0.01) and decreased the TXB2 and GPIIb/IIIa concentrations (plessthan 0.05,plessthan 0.01) in rat platelets. GAG significantly enhanced the phosphorylation levels of PKA and VASP in rat platelets plessthan 0.01) and had a synergistic effect with the P2Y12 receptor blocker. GAG significantly reduced the expression level of P2Y12 gene in rat platelets (plessthan 0.01). We speculated that GAG from U. unicinctus inhibited platelet aggregation in rats through the P2Y12 receptor signaling pathway.

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Rocuronium Has a Suppressive Effect on Platelet Function via the P2Y12 Receptor Pathway In Vitro That Is Not Reversed by Sugammadex

International Journal of Molecular Sciences ◽

10.3390/ijms21176399 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6399

Author(s):

Yutaka Murata ◽

Shuji Kawamoto ◽

Kazuhiko Fukuda

Keyword(s):

Platelet Aggregation ◽

Muscle Relaxation ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Suppressive Effect ◽

P2y12 Receptor ◽

Receptor Signaling Pathway ◽

Morpholine Ring ◽

Platelet Functions

Rocuronium is an aminosteroid nondepolarizing neuromuscular blocker that is widely used for anesthesia and intensive care. In this study, we investigated the effect of rocuronium on human platelet functions in vitro. The effects of rocuronium on platelet aggregation, P-selectin expression, and cyclic adenosine monophosphate (cAMP) levels in platelets were measured using an aggregometer, an enzyme immunoassay, and flow cytometry, respectively. Rocuronium inhibited ADP-induced platelet aggregation, P-selectin expression and suppression of cAMP production. These effects were not antagonized by equimolar sugammadex, a synthetic γ-cyclodextrin derivative that antagonizes rocuronium-induced muscle relaxation by encapsulating the rocuronium molecule. Morpholine, which constitutes a part of the rocuronium molecule but is not encapsulated by sugammadex, inhibited ADP-induced platelet aggregation. Vecuronium, which has a molecular structure similar to that of rocuronium but does not possess a morpholine ring, had no significant effect on ADP-induced platelet aggregation. These results indicate that rocuronium has a suppressive effect on platelet functions in vitro that is not reversed by sugammadex and suggest that this effect is mediated by blockade of the P2Y12 receptor signaling pathway via the morpholine ring of rocuronium.

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