Inhibition of activity of GABA transporter GAT1 by δ-opioid receptor
- Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR) activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na(+)-dependent [(3)H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.
Author: | Lu Pu, Nanjie Xu, Peng Xia, Quanbao Gu, Shuanglai Ren, Thomas Fucke, Gang Pei, Wolfgang Schwarz |
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URN: | urn:nbn:de:hebis:30:3-289589 |
DOI: | https://doi.org/10.1155/2012/818451 |
ISSN: | 1741-4288 |
ISSN: | 1741-427X |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/23365600 |
Parent Title (English): | Evidence-based complementary and alternative medicine : eCAM |
Publisher: | Hindawi |
Place of publication: | New York, NY |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2012/12/25 |
Date of first Publication: | 2012/12/25 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2013/02/25 |
Volume: | 2012 |
Issue: | Article ID 818451 |
Page Number: | 12 |
Note: | Copyright © 2012 Lu Pu et al. This is an open access article distributed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
HeBIS-PPN: | 332506304 |
Institutes: | Physik / Physik |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Sammlung Biologie / Sondersammelgebiets-Volltexte | |
Licence (German): | ![]() |