{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:33:45Z","timestamp":1770910425754,"version":"3.50.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,5,1]]},"abstract":"<jats:p> We have confirmed that A6 cells (derived from kidney of Xenopus laevis), which contain both mineralocorticoid and glucocorticoid receptors, do not normally possess 11\u03b2-hydroxysteroid dehydroxgenase (11\u03b2-HSD1 or 11\u03b2-HSD2) enzymatic activity and so are without apparent \u201cprotective\u201d enzymes. A6 cells do not convert the glucocorticoid corticosterone to 11-dehydrocorticosterone but do, however, possess steroid 6\u03b2-hydroxylase that transforms corticosterone to 6\u03b2-hydroxycorticosterone. This hydroxylase is cytochrome P-450 3A (CYP3A). We have now determined the effects of 3\u03b1,5\u03b2-tetrahydroprogesterone and chenodeoxycholic acid (both inhibitors of 11\u03b2-HSD1) and 11-dehydrocorticosterone and 11\u03b2-hydroxy-3\u03b1,5\u03b2-tetrahydroprogesterone (inhibitors of 11\u03b2-HSD2) and carbenoxalone, which inhibits both 11\u03b2-HSD1 and 11\u03b2-HSD2, on the actions and metabolism of corticosterone and active Na<jats:sup>+<\/jats:sup> transport [short-circuit current ( I <jats:sub>sc<\/jats:sub>)] in A6 cells. All of these 11\u03b2-HSD inhibitory substances induced a significant increment in corticosterone-induced I <jats:sub>sc<\/jats:sub>, which was detectable within 2 h. However, none of these agents caused an increase in I <jats:sub>sc<\/jats:sub> when incubated by themselves with A6 cells. In all cases, the additional I <jats:sub>sc<\/jats:sub> was inhibited by the mineralocorticoid receptor (MR) antagonist, RU-28318, whereas the original I <jats:sub>sc<\/jats:sub>elicited by corticosterone alone was inhibited by the glucocorticoid receptor antagonist, RU-38486. In separate experiments, each agent was shown to significantly inhibit metabolism of corticosterone to 6\u03b2-hydroxycorticosterone in A6 cells, and a linear relationship existed between 6\u03b2-hydroxylase inhibition and the MR-mediated increase in I <jats:sub>sc<\/jats:sub>in the one inhibitor tested. Troleandomycin, a selective inhibitor of CYP3A, inhibited 6\u03b2-hydroxylase and also significantly enhanced corticosterone-induced I <jats:sub>sc<\/jats:sub> at 2 h. These experiments indicate that the enhanced MR-mediated I <jats:sub>sc<\/jats:sub> in A6 cells may be related to inhibition of 6\u03b2-hydroxylase activity in these cells and that this 6\u03b2-hydroxylase (CYP3A) may be protecting the expression of corticosterone-induced active Na<jats:sup>+<\/jats:sup> transport in A6 cells by MR-mediated mechanism(s). <\/jats:p>","DOI":"10.1152\/ajpcell.1998.274.5.c1245","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:23:41Z","timestamp":1514136221000},"page":"C1245-C1252","source":"Crossref","is-referenced-by-count":28,"title":["A second enzyme protecting mineralocorticoid receptors  from glucocorticoid occupancy"],"prefix":"10.1152","volume":"274","author":[{"given":"David J.","family":"Morris","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The Miriam Hospital, Lifespan, and Brown University School of Medicine, Providence, Rhode Island 02903;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed A.","family":"Latif","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, The Miriam Hospital, Lifespan, and Brown University School of Medicine, Providence, Rhode Island 02903;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Rokaw","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles O.","family":"Watlington","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Medical College of Virginia, Richmond, Virginia 23298"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-111-5-1683"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.284"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1989.257.4.F700"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1993.264.5.F854"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1042\/bj1070239"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.257.4.C665"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.421"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1988.255.4.F736"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)90742-8"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(94)90283-6"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/science.2845584"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1989.257.4.F690"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(93)90136-O"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/endo-116-3-1189"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.258.3.C480"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(92)90042-X"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(94)90084-1"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(89)90092-5"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.19.6056"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(94)90001-9"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-128X(96)00208-5"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/S0083-6729(08)60447-1"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(90)90084-O"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1990.258.3.F756"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-394"},{"key":"B26","first-page":"85","volume":"50","author":"New M. 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