{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T03:33:04Z","timestamp":1789270384057,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4385,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1997,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The loop diuretic furosemide is known to antagonize the function of \u03b3\u2010aminobutyric acid type A (GABA<jats:sub>A<\/jats:sub>) receptors. The purpose of the present study was to examine the direct interaction of furosemide with the GABA<jats:sub>A<\/jats:sub> receptors by autoradiography and ligand binding studies with native rat and human receptors and with recombinant receptors composed of rat subunits.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Autoradiography with [<jats:sup>35<\/jats:sup>S]\u2010<jats:italic>t<\/jats:italic>\u2010butylbicyclophosphorothionate ([<jats:sup>35<\/jats:sup>S]\u2010TBPS) as a ligand indicated that furosemide (0.1\u20131 m<jats:sc>m<\/jats:sc>) reversed the 5 \u03bc<jats:sc>m<\/jats:sc> GABA\u2010induced inhibition of binding only in the cerebellar granule cell layer of rat brain sections. In all other regions studied, notably also in the hippocampal and thalamic areas, furosemide failed to antagonize GABA. Furosemide 1 m<jats:sc>m<\/jats:sc> decreased [<jats:sup>35<\/jats:sup>S]\u2010TBPS binding only in a limited number of brain regions, but facilitation of the GABA\u2010inhibition of the binding was much more widespread.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In well\u2010washed rat cerebellar, but not cerebrocortical, membranes, furosemide enhanced the [<jats:sup>35<\/jats:sup>S]\u2010TBPS binding over basal level in the absence of added GABA. The GABA<jats:sub>A<\/jats:sub> antagonist, SR 95531, and the convulsant, Ro 5\u20134864, blocked this furosemide\u2010induced increase. Both interactions with the furosemide enhancement are likely to be allosteric, since furosemide affected the binding of [<jats:sup>3<\/jats:sup>H]\u2010SR 95531 and [<jats:sup>3<\/jats:sup>H]\u2010Ro 5\u20134864 identically in the cerebellar and cerebrocortical membranes. Maximal GABA\u2010antagonism induced by furosemide in cerebellar membranes was further increased by SR 95531 but not by Ro 5\u20134864, indicating additive antagonism only for SR 95531. In human cerebellar receptors, only GABA antagonism by furosemide, but not the enhancement without added GABA, was observed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In recombinant GABA<jats:sub>A<\/jats:sub> receptors, furosemide antagonism of GABA\u2010inhibition of [<jats:sup>35<\/jats:sup>S]\u2010TBPS binding depended only on the presence of \u03b16 and \u03b22\/3 subunits, irrespective of the presence or absence of \u03b32 or \u03b4 subunits.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In \u03b16\u03b23\u03b32 receptors, clozapine reversed the enhancement of [<jats:sup>35<\/jats:sup>S]\u2010TBPS binding by furosemide in the absence of GABA. However, it failed to affect the GABA\u2010antagonism of furosemide, suggesting that the enhancement of basal binding and the GABA antagonism might represent two different allosteric actions of furosemide.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, the present results indicate that furosemide is a subtype\u2010selective GABA<jats:sub>A<\/jats:sub> antagonist with a mode of action not shared by several other antagonists, which makes furosemide a unique compound for development of potential GABA<jats:sub>A<\/jats:sub> receptor subtype\u2010specific and \u2010selective ligands.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>120<\/jats:bold>, 741\u2013748; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0700922\">10.1038\/sj.bjp.0700922<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0700922","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T16:10:42Z","timestamp":1156522242000},"page":"741-748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Furosemide interactions with brain GABA<sub>A<\/sub> receptors"],"prefix":"10.1111","volume":"120","author":[{"given":"Esa R","family":"Korpi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"L\u00fcddens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"463","article-title":"Electrophysiological actions of Ro 5\u20134864 on cerebellar Purkinje neurons: evidence for \u2018peripheral\u2019 benzodiazepine receptor\u2010mediated depression","volume":"248","author":"Basile A.S.","year":"1989","journal-title":"J. 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