The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function.

Abstract:

:The present study examined the potential membrane retention of desipramine (DMI) following exposures of 293-hNET cells to DMI, and its effect on [3H]NE uptake. Incubation of cells with 500 nM DMI for 1 h or 1 day persistently inhibited the uptake of [3H]NE up to 7 days, despite daily repeated washing of cells with drug-free medium. Uptake inhibition was paralleled by persistent retention of DMI associated with cells, as determined by HPLC and by radiotracer experiments using [3H]DMI. [3H]DMI trapped in membranes was displaceable by the structurally unrelated NET inhibitor, nisoxetine, in a concentration-dependent manner, implying interaction of retained [3H]DMI with the NET. A similar cellular retention was observed following incubation of cells with nisoxetine. The results demonstrate that DMI and nisoxetine are persistently retained in cell membranes, at least partly in association with the NET. The retention and slow diffusion of DMI and nisoxetine from membranes may contribute to their pharmacological and modulatory action on NET.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Zhu MY,Kyle PB,Hume AS,Ordway GA

doi

10.1023/b:nere.0000013747.04964.46

keywords:

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

419-27

issue

2

eissn

0364-3190

issn

1573-6903

journal_volume

29

pub_type

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