Effects of ketamine on exocytotic and non-exocytotic noradrenaline release.
To characterise ketamine-induced sympathomimetic action, we examined the effects of ketamine on in vivo cardiac sympathetic nerve endings function. Using adult cats given anaesthesia with pentobarbital, dialysis probes were implanted in the left ventricular myocardium and dialysate noradrenaline (NA) concentrations were measured as an indicator of NA output at the cardiac sympathetic nerve endings. Ketamine was locally administered through the dialysis probe, and dialysate NA responses were obtained in the following conditions. (1) In the resting state, ketamine (10 mM) increased dialysate NA concentration. This increase in dialysate NA was not altered by addition of omega-conotoxin GVIA (N-type Ca(2+) channel blocker) or desipramine (membrane NA uptake blocker). (2) Sympathetic activation by electrical stimulation of the stellate ganglia (ES-SG; exocytotic NA release): ES-SG caused an increase in dialysate NA, which was further augmented by addition of desipramine. During co-administration of desipramine and ketamine, dialysate NA response to ES-SG was smaller than with desipramine alone. Further, there was no significant difference in the dialysate NA response to ES-SG between ketamine and ketamine + desipramine. These data suggested that both exocytosis and NA uptake function were impaired by ketamine. (3) Non-exocytotic NA release by ouabain: ouabain caused increases in dialysate NA. These increases in dialysate NA were suppressed by ketamine, which impaired the membrane outward NA transport evoked by ouabain. We conclude that ketamine impaired exocytotic and non-exocytotic NA release. However, ketamine spontaneously evoked NA efflux that was independent of exocytosis and insensitive to NA transporter.
Kitagawa
Hirotoshi
H
Department of Anesthesia, Nagahama City Hospital, Nagahama, Japan. hirotosi@belle.shiga-med.ac.jp
Yamazaki
Toji
T
Akiyama
Tsuyoshi
T
Mori
Hidezo
H
Sunagawa
Kenji
K
D000818:Animals; D002415:Cats; D004558:Electric Stimulation; D005089:Exocytosis / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology
D010042:Ouabain; D007649:Ketamine; D009638:Norepinephrine