KETAMINE INHIBITS MONOAMINE TRANSPORTERS EXPRESSED IN HUMAN EMBRYONICKIDNEY-293 CELLS

Background: Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibilit y that ketamine affects monoaminergic neurotransmission, To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, d opamine, and serotonin transporters and investigated the effects of ke tamine on these transporters. Methods: Human embryonic kidney cells we re transfected using the Chen-Okayama method with the human norepineph rine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbita l. Results: Inhibition analysis showed that ketamine significantly inh ibited the uptake of all three monoamine transporters in a dose-depend ent manner, The Ki (inhibition constant) values of ketamine on the nor epinephrine, dopamine, and serotonin transporters were 66.8 mu M, 62.9 mu M, and 162 mu M, respectively. Pentobarbital, a typical general an esthetic agent with no psychotic symptom, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor t he glutamate/aspartate transporter was affected by ketamine, indicatin g that ketamine preferentially inhibits monoamine transporters. Conclu sions: Ketamine inhibited monoamine transporters expressed in human em bryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might c ontribute to its psychotomimetic and sympathomimetic effects through p otentiating monoaminergic neurotransmission.