Ketamine inhibits inositol 1,4,5-trisphosphate production depending on the extracellular Ca2+ concentration in neonatal rat cardiomyocytes.
We investigated the effect of ketamine on inositol 1,4,5-trisphosphate (IP3) formation in rat cardiomyocytes. After the addition of 1 micromol/L ketamine, IP3 production in the presence of 0.5, 1, 5, 10, and 30 mmol/L Ca2+ significantly decreased from 537.1+/-8.3, 590.7+/-12.9, 690.6+/-7.9, 754.8+/-12.5, and 823.7+/-15.2 pmol/mg protein to 467.0+/-8.3, 483.8+/-11.0, 512.6+/-21.3, 612.1+/-16.9, and 652.6+/-17.3 pmol/mg protein, respectively. When exposed to TMB-8 (a intracellular calcium inhibitor), IP3 production decreased significantly from 347.2+/-27.3 to 283.8+/-20.4 pmol/mg protein in the presence of 1 micromol/L ketamine, but A23187, which increases intracellular calcium, did not affect the inhibition of IP3 production by ketamine. These results demonstrate that ketamine decreases IP3 formation through inhibition of the calcium ion-sensing receptor and that IP3 formation reduced by ketamine is not affected by the alteration of intracellular calcium.


CONCLUSIONS
Ketamine has a negative inotropic effect in isolated cardiomyocytes. The negative inotropic effect was associated with a decrease in inositol 1,4,5-trisphosphate production, and the inhibitory action was enhanced depending on the concentration of extracellular Ca2+.
Kudoh
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Department of Anesthesiology, University of Hirosaki School of Medicine, Aomori, Japan.
Matsuki
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D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D007649:Ketamine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats
D000778:Anesthetics, Dissociative; D002121:Calcium Channel Blockers; D000001:Calcimycin; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D007649:Ketamine; D015544:Inositol 1,4,5-Trisphosphate; D001920:Bradykinin; D002118:Calcium