{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T12:59:33Z","timestamp":1791118773978,"version":"4.1.0"},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,3,15]]},"abstract":"<jats:p>To elucidate the mechanism of action of aldosterone antagonists, we studied the interaction of spironolactone with the chick mineralocorticosteroid receptor (MR). Intestinal cytosol contains specific spironolactone-binding sites (Kd approximately 3 nM; max. no. of binding sites approximately 100 fmol\/mg of protein) that have been identified as MRs by competition experiments with steroid ligands and with the monoclonal anti-idiotypic antibody H10E that interacts with aldosterone-binding domain of the MR. Binding studies indicate that aldosterone and spironolactone bind to the MR through a common site that encompasses the epitope recognized by H10E. At 4 degrees C, spironolactone dissociates much more rapidly from the cytosol 8-9 S form of MR (t1\/2 38 min) than does aldosterone (t1\/2 3240 min). A high dissociation rate was also observed for progesterone, a natural aldosterone antagonist (t1\/2 84 min). The covalent linkage of the 90 kDa heat shock protein (hsp90) to the ligand-binding subunit of MR with dimethyl pimelimidate did not notably modify the rate of dissociation of spironolactone from the receptor (t1\/2 96 min), excluding the possibility that the rapid dissociation rate of the antagonist was related to hsp90 release. The effects of aldosterone and the two anti-mineralocorticosteroids on the 8-9 S heterooligomeric structure of the MR differed strikingly. Using low-salt density-gradient centrifugation analysis, aldosterone-labelled receptors were recovered as 8-9S complexes, whereas 4 S entities were detected after spironolactone and progesterone binding. This indicated that, under the experimental conditions used, aldosterone antagonists facilitate hsp90 release and thus do not stabilize the non-DNA-binding 8-9S form of MR. We propose that the combination of rapid dissociation of the ligand and a weakened hsp90-receptor interaction is involved in the anti-mineralococorticosteroid activity of aldosterone antagonists.<\/jats:p>","DOI":"10.1042\/bj2820697","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:25:44Z","timestamp":1439241944000},"page":"697-702","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Aldosterone antagonists destabilize the mineralocorticosteroid receptor"],"prefix":"10.1042","volume":"282","author":[{"given":"B","family":"Couette","sequence":"first","affiliation":[{"name":"Lab. Hormones, INSERM U 33 and Facult\u00e9 de M\u00e9decine, 94276 Bic\u00eatre Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Lombes","sequence":"additional","affiliation":[{"name":"Lab. Hormones, INSERM U 33 and Facult\u00e9 de M\u00e9decine, 94276 Bic\u00eatre Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E E","family":"Baulieu","sequence":"additional","affiliation":[{"name":"Lab. Hormones, INSERM U 33 and Facult\u00e9 de M\u00e9decine, 94276 Bic\u00eatre Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M E","family":"Rafestin-Oblin","sequence":"additional","affiliation":[{"name":"Lab. Hormones, INSERM U 33 and Facult\u00e9 de M\u00e9decine, 94276 Bic\u00eatre Cedex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/282\/3\/697\/606180\/bj2820697.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/282\/3\/697\/606180\/bj2820697.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T21:47:13Z","timestamp":1637704033000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/282\/3\/697\/27715\/Aldosterone-antagonists-destabilize-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,3,15]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1992,3,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj2820697","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,3,15]]}}}