{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:06:51Z","timestamp":1791306411171,"version":"4.3.1"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":2589,"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":[[2002,1]]},"abstract":"\n \n \n \n The action of the \u03b2\u2010lactam antibiotics, penicillin\u2010G (PCG) and cefoselis (CFSL) on GABA\n A<\/jats:sub>\n receptors (GABA\n A<\/jats:sub>\n \u2010R) was investigated using the two\u2010electrode voltage clamp technique and\n Xenopus<\/jats:italic>\n oocyte expressed murine GABA\n A<\/jats:sub>\n \u2010R.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Murine GABA\n A<\/jats:sub>\n \u2010Rs were expressed in\n Xenopus<\/jats:italic>\n oocytes by injecting cRNA that encoded for each subunit (\u03b11, \u03b22, and \u03b32) and the effects of PCG and CFSL on the \u03b11\u03b22\u03b32s subunit receptors were examined using two\u2010electrode voltage clamp. Using the \u03b11\u03b22\u03b32s GABA\n A<\/jats:sub>\n \u2010R, PCG and CFSL inhibited GABA\u2010induced currents in a concentration\u2010dependent manner, with IC\n 50<\/jats:sub>\n s of 557.1\u00b1125.4 and 185.0\u00b126.6\u2003\u03bc\n M<\/jats:sc>\n , respectively. The inhibitory action of PCG on GABA\u2010induced currents was non\u2010competitive whereas that of CFSL was competitive.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Mutation of tyrosine to phenylalanine at position 256 in the \u03b22 subunit (\u03b22\n Y256F<\/jats:sub>\n ), which is reported to abolish the inhibitory effect of picrotoxin, drastically reduced the potency of PCG (IC\n 50<\/jats:sub>\n =28.4\u00b11.42\u2003m\n M<\/jats:sc>\n ) for the \u03b11\u03b22\n Y256F<\/jats:sub>\n \u03b32s receptor without changing the IC\n 50<\/jats:sub>\n of CFSL (189\u00b126.6\u2003\u03bc\n M<\/jats:sc>\n ).\n <\/jats:p>\n <\/jats:list-item>\n \n \n These electrophysiological data indicate that PCG and CFSL inhibit GABA\n A<\/jats:sub>\n \u2010R in a different manner, with PCG acting non\u2010competitively and CFSL competitively. The mutational study indicates that PCG might act on an identical or nearby site to that of picrotoxin in the channel pore of the GABA\n A<\/jats:sub>\n \u2010R.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n \n British Journal of Pharmacology<\/jats:italic>\n (2001)\n 135<\/jats:bold>\n , 427\u2013432; doi:\n 10.1038\/sj.bjp.0704496<\/jats:ext-link>\n <\/jats:p>","DOI":"10.1038\/sj.bjp.0704496","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T16:40:49Z","timestamp":1106930449000},"page":"427-432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["The\n \u03b2<\/i>\n \u2010lactam antibiotics, penicillin\u2010G and cefoselis have different mechanisms and sites of action at GABA\n A<\/sub>\n receptors"],"prefix":"10.1111","volume":"135","author":[{"given":"Masahiro","family":"Sugimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakae","family":"Fukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kayakiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuya","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"291","article-title":"International Union of Pharmacology. 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