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- Title
Up-regulation of noradrenaline transporter in response to prolonged exposure to ketamine.
- Authors
Hara, Koji; Minami, Kouichiro; Ueno, Susumu; Toyohira, Yumiko; Tsutsui, Masato; Shigematsu, Akio; Yanagihara, Nobuyuki
- Abstract
We previously reported that the intravenous anaesthetic ketamine acutely inhibits the activity of the noradrenaline transporter (NAT) by acting on a site partly overlapping the desipramine binding site. Here we report the effects of a prolonged exposure to ketamine on the functional activity and number of NAT and its mRNA in cultured bovine adrenal medullary cells. Treatment of cells with ketamine (10–1000 µM) for 1–24 h resulted in a transient decrease and subsequent increase in [3H]noradrenaline (NA) uptake by the cells. Saturation analysis showed that ketamine (100 µM, 12 h) increased the Vmax value of [3H]NA uptake without any change in the Km value. Ketamine also increased the specific binding of [3H]nisoxetine to plasma membranes isolated from the cells. Scatchard analysis of [3H]nisoxetine binding revealed that ketamine increased the Bmax value without altering the Kd value, suggesting an increase in the number of NAT in the plasma membrane. The stimulatory effect of ketamine on [3H]NA uptake was blocked by cycloheximide, an inhibitor of protein synthesis. Treatment of cells with ketamine for 12–24 h enhanced the expression of NAT mRNA. The present findings demonstrated that prolonged exposure to ketamine increases the functional activity of NAT and its mRNA. This may imply that ketamine negatively modulates sympathetic nervous activity through an up-regulation of NAT during long anaesthesia.
- Subjects
MESSENGER RNA; NEUROTRANSMITTERS; CATECHOLAMINES; CELL membranes; ANESTHESIA; PROTEIN synthesis
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2002, Vol 365, Issue 5, p406
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-002-0534-1