{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T14:21:53Z","timestamp":1725373313747},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2950,"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":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Human GABA<jats:sub>A<\/jats:sub> receptors containing different \u03b1 and \u03b2 subunits with or without the \u03b32S or \u03b32L subunits were expressed in <jats:italic>Xenopus<\/jats:italic> oocytes and the effects of the insecticides \u03b3\u2010 and \u03b4\u2010hexachlorocyclohexane (\u03b3\u2010HCH and \u03b4\u2010HCH, respectively) on these receptor subunit combinations were examined using two electrode voltage\u2010clamp procedures.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u03b3\u2010HCH produced incomplete inhibition of GABA responses on all receptor combinations examined with affinities in the range of 1.1\u2003\u2013\u20031.9\u2003\u03bc<jats:sc>M<\/jats:sc>. Affinity was not dependent on subunit composition but the maximum percentage of inhibition was significantly reduced in \u03b21\u2010containing receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>\u03b4\u2010HCH both potentiated GABA<jats:sub>A<\/jats:sub> receptors and activated them in the absence of GABA at concentrations higher than those producing potentiation. Allosteric enhancement of GABA<jats:sub>A<\/jats:sub> receptor function by \u03b4\u2010HCH was not affected by the subunit composition of the receptor, By contrast the GABA mimetic actions of \u03b4\u2010HCH were abolished in receptors containing either \u03b14, \u03b21 or \u03b32L subunits.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sensitivity to the direct actions were not restored in receptors containing the mutant \u03b21(S290N) subunit, but \u03b11\u03b22\u03b32L receptors became sensitive to the direct actions of \u03b4\u2010HCH when oocytes were treated for 24\u2003h with the protein kinase inhibitor isoquinolinesulphonyl\u20102\u2010methyl piperazine dihydrochloride (H\u20107).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We have shown the influence of various \u03b1, \u03b2 and \u03b3 subunits on the inhibitory, GABA mimetic and allosteric effects of HCH isomers. The data reveal that neither the inhibitory actions of \u03b3\u2010HCH nor the allosteric effects \u03b4\u2010HCH has a strict subunit dependency. By contrast, sensitivity to the direct actions of \u03b4\u2010HCH are abolished in receptors containing \u03b14, \u03b21 or \u03b32L subunits.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 205\u2013212; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703824\">10.1038\/sj.bjp.0703824<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703824","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:06:00Z","timestamp":1106946360000},"page":"205-212","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of \u03b3\u2010HCH and \u03b4\u2010HCH on human recombinant GABA<sub>A<\/sub> receptors: dependence on GABA<sub>A<\/sub> receptor subunit combination"],"prefix":"10.1111","volume":"132","author":[{"given":"P D","family":"Maskell","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K A","family":"Wafford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Bermudez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"411","article-title":"A single hydrophobic residue confers barbiturate sensitivity to \u03b3\u2010aminobutyric acid type C receptor","volume":"55","author":"AMIN J.","year":"1999","journal-title":"Mol. 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