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 Resjournal_title
Neurochemical researchauthors
Zhu MY,Kyle PB,Hume AS,Ordway GAdoi
10.1023/b:nere.0000013747.04964.46keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
419-27issue
2eissn
0364-3190issn
1573-6903journal_volume
29pub_type
杂志文章abstract::The secretion of fluid and electrolytes by salivary gland acinar cells requires the coordinated regulation of multiple ion channel and transporter proteins, signaling components, and water transport. Importantly, neurotransmitter stimulated increase in the cytosolic free [Ca(2+)] ([Ca(2+)](i)) is critical for the regu...
journal_title:Neurochemical research
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journal_title:Neurochemical research
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Neurochemical research
pub_type: 杂志文章
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