{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T14:08:42Z","timestamp":1698588522838},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"4","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,4]]},"abstract":"<jats:p>Barlow JW, Curtis AJ, Raggatt LE, Loidl NM, Topliss DJ. Stockigt JR. Drug competition for intracellular triiodothyronine-binding sites. Eur J Endocrinol 1944;130:417\u201321. ISSN 0804\u20134643<\/jats:p>\n        <jats:p>A variety of substances, including frusemide, non-esterified fatty acids (NEFAs) and non-steroidal antiinflammatory drugs (NSAIDs), can compete for triiodothyronine (T<jats:sub>3<\/jats:sub>)-binding sites in serum and at the cell surface. We examined the competitive potency of these agents at intracellular T<jats:sub>3<\/jats:sub>-binding sites in order to assess their potential to act as T<jats:sub>3<\/jats:sub> antagonists. Competition for [<jats:sup>125<\/jats:sup>I]T<jats:sub>3<\/jats:sub> binding was determined using hydroxyapatite separation in cytosols and nuclear extracts prepared from livers of <jats:italic>Macaca fascicularis<\/jats:italic>. The T<jats:sub>3<\/jats:sub> affinities were 15.8 \u00b1 1.2 nmol\/l in cytosol and 0.23 \u00b1 0.02 nmol\/l in nuclear extract. Does\u2013response curves were analysed by a four-parameter sigmoid curve-fitting program to determine competitor potency. The nineteen agents tested included various NSAIDs, NEFAs, non-bile acid cholephils (NBACs), frusemide, amiodarone and the flavonoid EMD 21388. In nuclear extract the most active competitors were linoleic acid (8.5 \u03bcmol\/l) and linolenic acid (7.8 \u03bcmol\/l), Potencies of NSAIDs varied between 66 \u03bcmol\/l (meclofenamic acid) and 525 \u03bcmol\/l (diclofenac). In cytosol, NEFAs were less potent but NSAIDs were stronger competitors than in nuclear extract. Half-inhibitory potencies in cytosol were between 13.2 \u03bcmol\/l (meclofenamic acid) and 63.1 \u03bcmol\/l (flufenamic acid). The NBAC bromosulphthalein was one of the most potent inhibitors in both cytosol and nuclear extract. When expressed relative to T<jats:sub>3<\/jats:sub>, diclofenac was a more effective competitor in cytosol than it was in nuclear extract. Amiodarone and EMD 21388 were without effect both in cytosol and nuclear extract. Frusemide (759 \u03bcmol\/l) was weakly active in cytosol only. The action of T<jats:sub>3<\/jats:sub> was assessed by measuring secretion of sex hormone-binding globulin (SHBG) in Hep-G2 cells. After 3 days with total T<jats:sub>3<\/jats:sub> (0.1 \u03bcmol\/l), SHBG was 155 \u00b1 15% of the control. Amiodarone (100 \u03bcmol\/l) and meclofenamic acid (100 \u03bcmol\/l) were cytotoxic. Bromosulphthalein (10 \u03bcmol\/l), one of the most potent competitors at both the cytoplasmic and the nuclear level, did not influence the T<jats:sub>3<\/jats:sub>-induced rise in SHBG secretion. None of the drugs tested affected the magnitude of maximal induction of SHBG by T<jats:sub>3<\/jats:sub>. Substances that compete for serum and cell surface T<jats:sub>3<\/jats:sub>-binding sites are also weak competitors for intracellular T<jats:sub>3<\/jats:sub>-binding proteins, although the heirarchy of potency differs. Frusemide and diclofenac, with a greater relative potency for cytosolic binding than nuclear binding, may have potential use in investigating the function of cytosolic T<jats:sub>3<\/jats:sub>-binding. Amiodarone shows no binding activity and is not a hormone antagonist in primate hepatic tissue.<\/jats:p>\n        <jats:p>John W Barlow, Ewen Downie Metabolic Unit, Alfred Hospital, Commercial Road, Melbourne, Victoria 3181, Australia<\/jats:p>","DOI":"10.1530\/eje.0.1300417","type":"journal-article","created":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T21:19:42Z","timestamp":1229375982000},"page":"417-421","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":8,"title":["Drug competition for intracellular triiodothyronine-binding sites"],"prefix":"10.1093","volume":"130","author":[{"given":"John W","family":"Barlow","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea J","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorna E","family":"Raggatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole M","family":"Loidl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan J","family":"Topliss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan R","family":"Stockigt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/130\/4\/eje_130_4_017.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/130\/4\/eje_130_4_017.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:18:45Z","timestamp":1676391525000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/130\/4\/417\/6754976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4]]},"references-count":0,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/eje.0.1300417","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4]]}}}