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...
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| creator | Schwarz, Wolfgang Fucke, Thomas Ren, Shuanglai Gu, Quanbao Xia, Peng Xu, Nanjie Pu, Lu Pei, Gang |
| description | 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 [3H]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. |
| doi_str_mv | 10.1155/2012/818451 |
| format | Article |
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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 [3H]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.</description><identifier>ISSN: 1741-427X</identifier><identifier>EISSN: 1741-4288</identifier><identifier>DOI: 10.1155/2012/818451</identifier><identifier>PMID: 23365600</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Activation ; Acupuncture ; Analgesia ; Brain ; Brain research ; Brain slice preparation ; Dopamine ; Experiments ; Inhibition ; Kinases ; Laboratory animals ; Narcotics ; Nervous system ; Neurosciences ; Neurotransmitters ; Oocytes ; Opioid receptors ; Opioids ; Pain ; Pain perception ; Periaqueductal gray area ; Proteins ; Rats ; Rodents ; Synaptosomes ; Translocation ; Xenopus ; γ-Aminobutyric acid</subject><ispartof>Evidence-based complementary and alternative medicine, 2012-01, Vol.2012 (2012), p.1-12</ispartof><rights>Copyright © 2012 Lu Pu et al.</rights><rights>Copyright © 2012 Lu Pu et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2012 Lu Pu et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-ffe53bda020afd80ac63b29282d309c08a20b4cd66b823285de32950328f38453</citedby><cites>FETCH-LOGICAL-c429t-ffe53bda020afd80ac63b29282d309c08a20b4cd66b823285de32950328f38453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543822/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543822/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23365600$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xia, Ying</contributor><contributor>Ying Xia</contributor><creatorcontrib>Schwarz, Wolfgang</creatorcontrib><creatorcontrib>Fucke, Thomas</creatorcontrib><creatorcontrib>Ren, Shuanglai</creatorcontrib><creatorcontrib>Gu, Quanbao</creatorcontrib><creatorcontrib>Xia, Peng</creatorcontrib><creatorcontrib>Xu, Nanjie</creatorcontrib><creatorcontrib>Pu, Lu</creatorcontrib><creatorcontrib>Pei, Gang</creatorcontrib><title>Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor</title><title>Evidence-based complementary and alternative medicine</title><addtitle>Evid Based Complement Alternat Med</addtitle><description>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 [3H]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.</description><subject>Activation</subject><subject>Acupuncture</subject><subject>Analgesia</subject><subject>Brain</subject><subject>Brain research</subject><subject>Brain slice preparation</subject><subject>Dopamine</subject><subject>Experiments</subject><subject>Inhibition</subject><subject>Kinases</subject><subject>Laboratory animals</subject><subject>Narcotics</subject><subject>Nervous system</subject><subject>Neurosciences</subject><subject>Neurotransmitters</subject><subject>Oocytes</subject><subject>Opioid receptors</subject><subject>Opioids</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Periaqueductal gray 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Med</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>2012</volume><issue>2012</issue><spage>1</spage><epage>12</epage><pages>1-12</pages><issn>1741-427X</issn><eissn>1741-4288</eissn><abstract>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 [3H]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.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>23365600</pmid><doi>10.1155/2012/818451</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Activation Acupuncture Analgesia Brain Brain research Brain slice preparation Dopamine Experiments Inhibition Kinases Laboratory animals Narcotics Nervous system Neurosciences Neurotransmitters Oocytes Opioid receptors Opioids Pain Pain perception Periaqueductal gray area Proteins Rats Rodents Synaptosomes Translocation Xenopus γ-Aminobutyric acid |
| title | Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor |
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