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Published on: June 11, 2020
Ketamine inhibits endotoxin-induced inositol 1,4,5-triphosphate in rat ventricular cardiomyocytes
Akira Kudoh1, Hiroshi Katagai, Tomoko Takazawa
1Department of Anesthesiology, Hirosaki National Hospital, 1 Tominocho, Hirosaki 036-8545, Aomori, Japan. masuika@cc.hirosaki-u.ac.jp
Objective:
To investigate the effect of ketamine on endotoxin modulation of inositol 1,4,5-triphosphate (IP3) formation in cardiomyocytes.
Design:
A prospective observational cell culture study.
Setting:
A research laboratory in the University of Hirosaki School of Medicine.
Materials:
Neonatal rat cardiomyocytes.
Intervention:
We investigated bradykinin-induced IP3 production in the presence of lipopolysaccharide (LPS) and the effect of ketamine on the LPS modulation of IP3 formation. The LPS modulation of IP3 formation was measured in the presence of BM13177 (a thromboxane A2 (TXA2) receptor inhibitor) or GDPbetaS (a GTP-binding protein inhibitor). U46619 (a TXA2 agonist)-induced IP3 production was measured in the presence of ketamine, and the ketamine modulation of U46619-induced IP3 production was measured in the presence of W7 (a Ca2+ releasing agent) and verapamil (a Ca2+ channel blocker).
Results:
One micromole ketamine significantly attenuated the LPS-induced IP3 production from 763.8+/-34.6 to 461.6+/-65.1 pmol mg protein(-1). Ten micromoles of BM13177 or 1 mM GDPbetaS significantly blocked LPS modulation of bradykinin-induced IP3 production from 786.0+/-33.8 to 218.6+/-21.6 and 226.8+/-25.4 pmol mg protein(-1). One micromole of ketamine significantly decreased U46619-induced IP3 production from 857.3+/-45.0 to 632.9+/-64.5 pmol mg(-1) protein. The ketamine inhibition of U46619-induced IP3 production was enhanced by W7 and inhibited by verapamil.
Conclusion:
Ketamine decreased LPS-induced IP3 formation and the ketamine inhibition was associated with inhibition of the TXA2-IP3 sequence. Inhibition of TXA2 by ketamine was associated with a decrease in intracellular Ca2+.
