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. 2020 Sep 3;21(17):6399.
doi: 10.3390/ijms21176399.

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

Yutaka Murata  1 , Shuji Kawamoto  1 , Kazuhiko Fukuda  1
Affiliations

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

Yutaka Murata et al. Int J Mol Sci. .

Abstract

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.

Keywords: P2Y12 receptor; cyclodextrin; morpholine; platelet; rocuronium; sugammadex.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structures of (A) rocuronium bromide; (B) vecuronium bromide; (C) rocuronium-sugammadex complex, based on a previous report [10]; (D) and morpholine.
Figure 2
Figure 2
Effects of rocuronium, vecuronium, sugammadex, and morpholine on human platelet aggregation induced by 5 μM adenosine diphosphate (ADP). (A) Rocuronium (ROC) in the absence and presence of equimolar sugammadex (SGX) (5–500 μM). * p < 0.05 vs. ROC (−), SGX (−). (B) Vecuronium (VEC; 5–5000 μM). (C) Sugammadex (SGX; 5–500 μM). (D) Morpholine (MOR; 10 μM–10 mM). * p < 0.05 vs. MOR (−). Data are expressed as the mean ± SD. Rocuronium and morpholine suppressed ADP-induced platelet aggregation, whereas vecuronium and sugammadex did not show significant effects. The suppressive effect of rocuronium was not abolished by equimolar sugammadex.
Figure 3
Figure 3
Effects of rocuronium (ROC; 0.5–500 μM) on surface P-selectin expression in platelets stimulated with 10 μM ADP in the presence and absence of equimolar sugammadex (SGX; 0.5–500 μM). Data are expressed as the mean ± SD of the ratio to the positive control (ROC (−), SGX (−), ADP (+)). * p < 0.05 vs. positive control. NS, not significant. Rocuronium suppressed P-selectin expression on the surface of ADP-stimulated platelets, and this was not significantly affected by equimolar sugammadex.
Figure 4
Figure 4
Effects of rocuronium (ROC; 500 μM) and sugammadex (SGX; 500 μM) on cyclic adenosine monophosphate (cAMP) formation in platelets stimulated with 5 μM ADP. Data are expressed as the mean ± SD. * p < 0.05 vs. ROC (−), SGX (−). Rocuronium reduced the suppression of cAMP production in ADP-stimulated platelets, which was not significantly affected by sugammadex. Sugammadex alone had no significant effect on cAMP formation.
Figure 5
Figure 5
Proposed mechanism of the suppressive effect of rocuronium on platelet functions. Rocuronium suppresses platelet functions via its morpholine ring by blockade of the P2Y12 receptor signaling pathway. The morpholine ring in rocuronium is not encapsulated by sugammadex.
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References

    1. Hirakata H., Hatano Y., Ushikubi F., Mori K., Narumiya S., Nakamura K. The Effect of Inhaled Anesthetics on the Platelet Aggregation and the Ligand-Binding Affinity of the Platelet Thromboxane A2 Receptor. Anesth. Analg. 1995;81:114–118. - PubMed
    1. Hirakata H., Ushikubi F., Toda H., Nakamura K., Sai S., Urabe N., Hatano Y., Narumiya S., Mori K. Sevoflurane inhibits human platelet aggregation and thromboxane A 2 formation, possibly by suppression of cyclooxygenase activity. Anesthesiology. 1996;85:1447–1453. doi: 10.1097/00000542-199612000-00027. - DOI - PubMed
    1. Hirakata H., Nakamura K., Sai S., Okuda H., Hatano Y., Urabe N., Mori K. Platelet aggregation is impaired during anaesthesia with sevoflurane but not with isoflurane. Can. J. Anaesth. 1997;44:1157–1161. doi: 10.1007/BF03013337. - DOI - PubMed
    1. Hirakata H., Nakamura K., Yokubol B., Toda H., Hatano Y., Urabe N., Mori K. Propofol Has Both Enhancing and Suppressing Eflects on Human Platelet Aggregation. Anesthesiology. 1999;91:1361–1369. doi: 10.1097/00000542-199911000-00028. - DOI - PubMed
    1. Nakagawa T., Hirakata H., Sato M., Nakamura K., Hatano Y., Nakamura T., Fukuda K. Ketamine suppresses platelet aggregation possibly by suppressed inositol triphosphate formation and subsequent suppression of cytosolic calcium increase. Anesthesiology. 2002;96:1147–1152. doi: 10.1097/00000542-200205000-00018. - DOI - PubMed

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