The Use of Inhibitors of GABA‐Transaminase for the Determination of GABA Turnover in Mouse Brain Regions: An Evaluation of Aminooxyacetic Acid and Gabaculine
: The accumulation of γ‐aminobutyric acid (GABA) after inhibition of GABA‐T (4‐aminobutyrate: 2‐oxoglutamate aminotransferase, EC 2.6.1.19) by various doses of aminooxyacetic acid (AOAA) and gabaculine was studied in four different regions of the mouse brain. The dose‐response curve for GABA accumul...
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Veröffentlicht in: | Journal of neurochemistry 1982-01, Vol.38 (1), p.57-66 |
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description | : The accumulation of γ‐aminobutyric acid (GABA) after inhibition of GABA‐T (4‐aminobutyrate: 2‐oxoglutamate aminotransferase, EC 2.6.1.19) by various doses of aminooxyacetic acid (AOAA) and gabaculine was studied in four different regions of the mouse brain. The dose‐response curve for GABA accumulation after treatment with AOAA was linear up to 10 mg/kg i.p., and then leveled off. The increase in GABA accumulation after gabaculine treatment was linear up to 100 mg/kg i.p. No further increase was observed with doses up to 300 mg/kg i.p. The selectivity of both GABA‐T inhibitors was assessed by measuring their effects on the content of free amino acids in mouse brain. Apart from the substantial increase in the GABA concentration, there were significant decreases in the content of glutamic acid, aspartic acid, alanine and glutamine, and an increase in ornithine content after administration of gabaculine. The same changes in amino acid content were observed after treatment with AOAA, but the level of lysine was also increased and the change in alanine level was biphasic. All these changes, however, were very small compared with the large increase in GABA level. A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed, and the validity of the two techniques is discussed. The effect of diazepam on GABA levels and on the gabaculine‐induced accumulation of GABA was studied. The results obtained with diazepam show that this method can provide valuable insight into the effects of drugs on GABAergic mechanisms in vivo. |
doi_str_mv | 10.1111/j.1471-4159.1982.tb10853.x |
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The dose‐response curve for GABA accumulation after treatment with AOAA was linear up to 10 mg/kg i.p., and then leveled off. The increase in GABA accumulation after gabaculine treatment was linear up to 100 mg/kg i.p. No further increase was observed with doses up to 300 mg/kg i.p. The selectivity of both GABA‐T inhibitors was assessed by measuring their effects on the content of free amino acids in mouse brain. Apart from the substantial increase in the GABA concentration, there were significant decreases in the content of glutamic acid, aspartic acid, alanine and glutamine, and an increase in ornithine content after administration of gabaculine. The same changes in amino acid content were observed after treatment with AOAA, but the level of lysine was also increased and the change in alanine level was biphasic. All these changes, however, were very small compared with the large increase in GABA level. A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed, and the validity of the two techniques is discussed. The effect of diazepam on GABA levels and on the gabaculine‐induced accumulation of GABA was studied. The results obtained with diazepam show that this method can provide valuable insight into the effects of drugs on GABAergic mechanisms in vivo.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.1982.tb10853.x</identifier><identifier>PMID: 7108535</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>4-Aminobutyrate Transaminase - antagonists & inhibitors ; Acetates - pharmacology ; Aminooxyacetic Acid - pharmacology ; Aminooxyacetic acid‐Gabaculine‐Benzodiazepine ; Animals ; Brain - drug effects ; Brain - metabolism ; Cyclohexanecarboxylic Acids - pharmacology ; Diazepam - pharmacology ; Dose-Response Relationship, Drug ; GABA turnover rate ; GABA‐transaminase ; gamma-Aminobutyric Acid - metabolism ; Male ; Mice ; Time Factors ; Transaminases - antagonists & inhibitors</subject><ispartof>Journal of neurochemistry, 1982-01, Vol.38 (1), p.57-66</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3687-febc7fd25396627b41fbd2ac4d3b4b570e1f75e603c3026b5cc282647934305a3</citedby><cites>FETCH-LOGICAL-c3687-febc7fd25396627b41fbd2ac4d3b4b570e1f75e603c3026b5cc282647934305a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.1982.tb10853.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.1982.tb10853.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7108535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bernasconi, R.</creatorcontrib><creatorcontrib>Maitre, L.</creatorcontrib><creatorcontrib>Martin, P.</creatorcontrib><creatorcontrib>Raschdorf, F.</creatorcontrib><title>The Use of Inhibitors of GABA‐Transaminase for the Determination of GABA Turnover in Mouse Brain Regions: An Evaluation of Aminooxyacetic Acid and Gabaculine</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>: The accumulation of γ‐aminobutyric acid (GABA) after inhibition of GABA‐T (4‐aminobutyrate: 2‐oxoglutamate aminotransferase, EC 2.6.1.19) by various doses of aminooxyacetic acid (AOAA) and gabaculine was studied in four different regions of the mouse brain. The dose‐response curve for GABA accumulation after treatment with AOAA was linear up to 10 mg/kg i.p., and then leveled off. The increase in GABA accumulation after gabaculine treatment was linear up to 100 mg/kg i.p. No further increase was observed with doses up to 300 mg/kg i.p. The selectivity of both GABA‐T inhibitors was assessed by measuring their effects on the content of free amino acids in mouse brain. Apart from the substantial increase in the GABA concentration, there were significant decreases in the content of glutamic acid, aspartic acid, alanine and glutamine, and an increase in ornithine content after administration of gabaculine. The same changes in amino acid content were observed after treatment with AOAA, but the level of lysine was also increased and the change in alanine level was biphasic. All these changes, however, were very small compared with the large increase in GABA level. A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed, and the validity of the two techniques is discussed. The effect of diazepam on GABA levels and on the gabaculine‐induced accumulation of GABA was studied. The results obtained with diazepam show that this method can provide valuable insight into the effects of drugs on GABAergic mechanisms in vivo.</description><subject>4-Aminobutyrate Transaminase - antagonists & inhibitors</subject><subject>Acetates - pharmacology</subject><subject>Aminooxyacetic Acid - pharmacology</subject><subject>Aminooxyacetic acid‐Gabaculine‐Benzodiazepine</subject><subject>Animals</subject><subject>Brain - drug effects</subject><subject>Brain - metabolism</subject><subject>Cyclohexanecarboxylic Acids - pharmacology</subject><subject>Diazepam - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>GABA turnover rate</subject><subject>GABA‐transaminase</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Time Factors</subject><subject>Transaminases - antagonists & inhibitors</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1982</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkU9uEzEYxS0EKmnhCEgWC3Yz-O84U4nFNJRQVEBC6dqyPR7qaGK39kxJdj0CN-BunAQPCdnjjf35_d6zrAfAa4xKnNfbdYmZwAXDvC5xPSfloDGac1pun4DZUXoKZggRUlDEyHNwmtIaIVyxCp-AE_GX5zPwa3Vr4U2yMHTwyt867YYQ0zQtm4vm9-PPVVQ-qY3zKkNdiHDIhvd2sHG6G1zw_2C4GqMPDzZC5-HnMGb-Iqp8_ma_Zyydw8bDywfVj0dbkzNC2O6UsYMzsDGuhcq3cKm0MmPvvH0BnnWqT_blYT8DNx8uV4uPxfXX5dWiuS4Mreai6Kw2omsJp3VVEaEZ7nRLlGEt1UxzgSzuBLcVooYiUmluDJmTiomaMoq4omfgzT73Lob70aZBblwytu-Vt_krUjBc14ygDJ7vQRNDStF28i66jYo7iZGc2pFrOVUgpwrk1I48tCO32fzq8MqoN7Y9Wg91ZP3dXv_herv7j2T56cuCC_oHd4Cgtw</recordid><startdate>198201</startdate><enddate>198201</enddate><creator>Bernasconi, R.</creator><creator>Maitre, L.</creator><creator>Martin, P.</creator><creator>Raschdorf, F.</creator><general>Blackwell Publishing Ltd</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>7X8</scope></search><sort><creationdate>198201</creationdate><title>The Use of Inhibitors of GABA‐Transaminase for the Determination of GABA Turnover in Mouse Brain Regions: An Evaluation of Aminooxyacetic Acid and Gabaculine</title><author>Bernasconi, R. ; Maitre, L. ; Martin, P. ; Raschdorf, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3687-febc7fd25396627b41fbd2ac4d3b4b570e1f75e603c3026b5cc282647934305a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1982</creationdate><topic>4-Aminobutyrate Transaminase - antagonists & inhibitors</topic><topic>Acetates - pharmacology</topic><topic>Aminooxyacetic Acid - pharmacology</topic><topic>Aminooxyacetic acid‐Gabaculine‐Benzodiazepine</topic><topic>Animals</topic><topic>Brain - drug effects</topic><topic>Brain - metabolism</topic><topic>Cyclohexanecarboxylic Acids - pharmacology</topic><topic>Diazepam - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>GABA turnover rate</topic><topic>GABA‐transaminase</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Time Factors</topic><topic>Transaminases - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bernasconi, R.</creatorcontrib><creatorcontrib>Maitre, L.</creatorcontrib><creatorcontrib>Martin, P.</creatorcontrib><creatorcontrib>Raschdorf, F.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bernasconi, R.</au><au>Maitre, L.</au><au>Martin, P.</au><au>Raschdorf, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Use of Inhibitors of GABA‐Transaminase for the Determination of GABA Turnover in Mouse Brain Regions: An Evaluation of Aminooxyacetic Acid and Gabaculine</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1982-01</date><risdate>1982</risdate><volume>38</volume><issue>1</issue><spage>57</spage><epage>66</epage><pages>57-66</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><abstract>: The accumulation of γ‐aminobutyric acid (GABA) after inhibition of GABA‐T (4‐aminobutyrate: 2‐oxoglutamate aminotransferase, EC 2.6.1.19) by various doses of aminooxyacetic acid (AOAA) and gabaculine was studied in four different regions of the mouse brain. The dose‐response curve for GABA accumulation after treatment with AOAA was linear up to 10 mg/kg i.p., and then leveled off. The increase in GABA accumulation after gabaculine treatment was linear up to 100 mg/kg i.p. No further increase was observed with doses up to 300 mg/kg i.p. The selectivity of both GABA‐T inhibitors was assessed by measuring their effects on the content of free amino acids in mouse brain. Apart from the substantial increase in the GABA concentration, there were significant decreases in the content of glutamic acid, aspartic acid, alanine and glutamine, and an increase in ornithine content after administration of gabaculine. The same changes in amino acid content were observed after treatment with AOAA, but the level of lysine was also increased and the change in alanine level was biphasic. All these changes, however, were very small compared with the large increase in GABA level. A method for estimating the rate of the GABA turnover in vivo by measuring the initial rate of GABA accumulation after administration of AOAA or gabaculine is proposed, and the validity of the two techniques is discussed. The effect of diazepam on GABA levels and on the gabaculine‐induced accumulation of GABA was studied. The results obtained with diazepam show that this method can provide valuable insight into the effects of drugs on GABAergic mechanisms in vivo.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>7108535</pmid><doi>10.1111/j.1471-4159.1982.tb10853.x</doi><tpages>10</tpages></addata></record> |
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subjects | 4-Aminobutyrate Transaminase - antagonists & inhibitors Acetates - pharmacology Aminooxyacetic Acid - pharmacology Aminooxyacetic acid‐Gabaculine‐Benzodiazepine Animals Brain - drug effects Brain - metabolism Cyclohexanecarboxylic Acids - pharmacology Diazepam - pharmacology Dose-Response Relationship, Drug GABA turnover rate GABA‐transaminase gamma-Aminobutyric Acid - metabolism Male Mice Time Factors Transaminases - antagonists & inhibitors |
title | The Use of Inhibitors of GABA‐Transaminase for the Determination of GABA Turnover in Mouse Brain Regions: An Evaluation of Aminooxyacetic Acid and Gabaculine |
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