Effect of lactic acid on l-glutamate uptake in cultured astrocytes: mechanistic considerations
Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit l-glutamate ( l-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit l-Glu uptake. Astrocyte cultures trea...
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| Veröffentlicht in: | Brain research 1997-03, Vol.750 (1), p.59-66 |
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| creator | Bender, Alex S Young, Laurence P Norenberg, Michael D |
| description | Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit
l-glutamate (
l-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit
l-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of
l-Glu uptake by 65%. HCl (pH 6.1) also inhibited
l-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on
l-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling with
d-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on
l-Glu uptake, indicating that swelling per se or free radicals, were not the factors in
l-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of
l-Glu release and a seven-fold increase of K
+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K
+ and
l-Glu release which may be a factor in the inhibition of
l-Glu uptake by lactic acid in astrocytes. |
| doi_str_mv | 10.1016/S0006-8993(96)01331-5 |
| format | Article |
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l-glutamate (
l-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit
l-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of
l-Glu uptake by 65%. HCl (pH 6.1) also inhibited
l-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on
l-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling with
d-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on
l-Glu uptake, indicating that swelling per se or free radicals, were not the factors in
l-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of
l-Glu release and a seven-fold increase of K
+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K
+ and
l-Glu release which may be a factor in the inhibition of
l-Glu uptake by lactic acid in astrocytes.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/S0006-8993(96)01331-5</identifier><identifier>PMID: 9098530</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Animals, Newborn ; Astrocyte ; Astrocytes - cytology ; Astrocytes - drug effects ; Astrocytes - metabolism ; Biological Transport - drug effects ; Cell swelling ; Cells, Cultured ; Cerebral Cortex - cytology ; Cerebral Cortex - metabolism ; Glutamate release ; Glutamate uptake ; Glutamic Acid - metabolism ; Hydrochloric Acid - pharmacology ; Hydrogen-Ion Concentration ; Hypothermia ; Kinetics ; Lactic acid ; Lactic Acid - pharmacology ; Potassium ion release ; Rats ; Temperature</subject><ispartof>Brain research, 1997-03, Vol.750 (1), p.59-66</ispartof><rights>1997 Elsevier Science B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-d2bf419d6d852fae348691903e60fa17fae360d6b4b52887088a898bc223103d3</citedby><cites>FETCH-LOGICAL-c438t-d2bf419d6d852fae348691903e60fa17fae360d6b4b52887088a898bc223103d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-8993(96)01331-5$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9098530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bender, Alex S</creatorcontrib><creatorcontrib>Young, Laurence P</creatorcontrib><creatorcontrib>Norenberg, Michael D</creatorcontrib><title>Effect of lactic acid on l-glutamate uptake in cultured astrocytes: mechanistic considerations</title><title>Brain research</title><addtitle>Brain Res</addtitle><description>Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit
l-glutamate (
l-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit
l-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of
l-Glu uptake by 65%. HCl (pH 6.1) also inhibited
l-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on
l-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling with
d-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on
l-Glu uptake, indicating that swelling per se or free radicals, were not the factors in
l-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of
l-Glu release and a seven-fold increase of K
+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K
+ and
l-Glu release which may be a factor in the inhibition of
l-Glu uptake by lactic acid in astrocytes.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Astrocyte</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Biological Transport - drug effects</subject><subject>Cell swelling</subject><subject>Cells, Cultured</subject><subject>Cerebral Cortex - cytology</subject><subject>Cerebral Cortex - metabolism</subject><subject>Glutamate release</subject><subject>Glutamate uptake</subject><subject>Glutamic Acid - metabolism</subject><subject>Hydrochloric Acid - pharmacology</subject><subject>Hydrogen-Ion Concentration</subject><subject>Hypothermia</subject><subject>Kinetics</subject><subject>Lactic acid</subject><subject>Lactic Acid - pharmacology</subject><subject>Potassium ion release</subject><subject>Rats</subject><subject>Temperature</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1L7TAUDKLofepPELISXfR50rRp4kbkou8Jggt1a0iTU43245qkgv_e1ntx6-p8zZyBGUKOGPxlwMTZPQCITCrFT5Q4BcY5y8otsmCyyjORF7BNFj-QPfInxtdp5FzBLtlVoGTJYUGerpoGbaJDQ1tjk7fUWO_o0NM2e27HZDqTkI6rZN6Q-p7asU1jQEdNTGGwnwnjOe3Qvpjex5luhz56h8EkP3UHZKcxbcTDTd0nj9dXD8v_2e3dv5vl5W1mCy5T5vK6KZhywskybwzyQgrFFHAU0BhWzSsBTtRFXeZSViClkUrWNs85A-74Pjle_12F4X3EmHTno8W2NT0OY9SVVBMHql-BrJSKczEDyzXQhiHGgI1eBd-Z8KkZ6DkA_R2Ant3VSujvAHQ58Y42AmPdofthbRyf7hfrO052fHgMOlqPvUXnwxSEdoP_ReEL8ZaVfw</recordid><startdate>19970307</startdate><enddate>19970307</enddate><creator>Bender, Alex S</creator><creator>Young, Laurence P</creator><creator>Norenberg, Michael D</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>19970307</creationdate><title>Effect of lactic acid on l-glutamate uptake in cultured astrocytes: mechanistic considerations</title><author>Bender, Alex S ; Young, Laurence P ; Norenberg, Michael D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-d2bf419d6d852fae348691903e60fa17fae360d6b4b52887088a898bc223103d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Astrocyte</topic><topic>Astrocytes - cytology</topic><topic>Astrocytes - drug effects</topic><topic>Astrocytes - metabolism</topic><topic>Biological Transport - drug effects</topic><topic>Cell swelling</topic><topic>Cells, Cultured</topic><topic>Cerebral Cortex - cytology</topic><topic>Cerebral Cortex - metabolism</topic><topic>Glutamate release</topic><topic>Glutamate uptake</topic><topic>Glutamic Acid - metabolism</topic><topic>Hydrochloric Acid - pharmacology</topic><topic>Hydrogen-Ion Concentration</topic><topic>Hypothermia</topic><topic>Kinetics</topic><topic>Lactic acid</topic><topic>Lactic Acid - pharmacology</topic><topic>Potassium ion release</topic><topic>Rats</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bender, Alex S</creatorcontrib><creatorcontrib>Young, Laurence P</creatorcontrib><creatorcontrib>Norenberg, Michael D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bender, Alex S</au><au>Young, Laurence P</au><au>Norenberg, Michael D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of lactic acid on l-glutamate uptake in cultured astrocytes: mechanistic considerations</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>1997-03-07</date><risdate>1997</risdate><volume>750</volume><issue>1</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><abstract>Elevated levels of lactic acid can be deleterious to CNS tissue. Lactic acid is known to cause astroglial swelling and since glial swelling has been shown to inhibit
l-glutamate (
l-Glu) uptake, we examined whether one of the actions of lactic acid is to inhibit
l-Glu uptake. Astrocyte cultures treated with lactic acid (25 mM; pH 6.1) showed an inhibition of
l-Glu uptake by 65%. HCl (pH 6.1) also inhibited
l-Glu uptake and this inhibition was potentiated by sodium lactate (25 mM). The inhibitory effect of lactic acid on
l-Glu uptake was partially reversible and the reversibility was enhanced by hypothermia. Blocking glial swelling with
d-mannitol, or treatment with antioxidants or hypothermia did not inhibit the effect of lactic acid on
l-Glu uptake, indicating that swelling per se or free radicals, were not the factors in
l-Glu uptake inhibition. Lactic acid induced a four-fold enhancement of
l-Glu release and a seven-fold increase of K
+ release. Our results suggest that lactic acid, by direct effect on pH, brings about a stimulation of K
+ and
l-Glu release which may be a factor in the inhibition of
l-Glu uptake by lactic acid in astrocytes.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>9098530</pmid><doi>10.1016/S0006-8993(96)01331-5</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Brain research, 1997-03, Vol.750 (1), p.59-66 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Animals, Newborn Astrocyte Astrocytes - cytology Astrocytes - drug effects Astrocytes - metabolism Biological Transport - drug effects Cell swelling Cells, Cultured Cerebral Cortex - cytology Cerebral Cortex - metabolism Glutamate release Glutamate uptake Glutamic Acid - metabolism Hydrochloric Acid - pharmacology Hydrogen-Ion Concentration Hypothermia Kinetics Lactic acid Lactic Acid - pharmacology Potassium ion release Rats Temperature |
| title | Effect of lactic acid on l-glutamate uptake in cultured astrocytes: mechanistic considerations |
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