ISSN:
1432-1912
Keywords:
Key words Adrenal medullary cells
;
[3H]Desipramine binding
;
Ketamine
;
Noradrenaline transporter
;
[3H]Noradrenaline uptake
;
Xenopus oocytes
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive noradrenaline transporter (NAT) were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NAT (bNAT). Incubation (1–3 h) of adrenal medullary cells with ketamine (10–300 µM) caused an increase in appearance of catecholamines in culture medium. Ketamine (10–1000 µM) inhibited desipramine-sensitive uptake of [3H] noradrenaline (NA) (IC50=97 µM). Saturation analysis showed that ketamine reduced V max of [3H]NA uptake without changing K m, indicating a non-competitive inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a competitive inhibition of [3H]NA uptake while a derivative of ketamine, phencyclidine, showed a mixed type of inhibition. Ketamine (10–1000 µM) also inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [3H]desipramine binding revealed that ketamine increased K d without altering B max, indicating a competitive inhibition. In transfected Xenopus oocytes expressing the bNAT, ketamine attenuated [3H]NA uptake with a kinetic characteristic similar to that of cultured adrenal medullary cells. These findings are compatible with the idea that ketamine non-competitively inhibits the transport of NA by interacting with a site which partly overlaps the desipramine binding site on the NAT.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005261
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