{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T13:35:48Z","timestamp":1770903348553,"version":"3.50.1"},"reference-count":29,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1998,2,1]]},"abstract":"<jats:p> Some cystic fibrosis transmembrane conductance regulator (CFTR) mutations, such as G551D, result in a correctly localized Cl<jats:sup>\u2212<\/jats:sup> channel at the cell apical membrane, albeit with markedly reduced function. Patch-clamp studies have indicated that both phosphatase inhibitors and 3-isobutyl-1-methylxanthine (IBMX) can induce Cl<jats:sup>\u2212<\/jats:sup> secretion through the G551D mutant protein. We have now assessed whether these agents can induce Cl<jats:sup>\u2212<\/jats:sup> secretion in cftr<jats:sup>G551D<\/jats:sup> mutant mice. No induction of Cl<jats:sup>\u2212<\/jats:sup>secretion was seen with the alkaline phosphatase inhibitors bromotetramisole or levamisole in either the respiratory or intestinal tracts of wild-type or cftr<jats:sup>G551D<\/jats:sup> mice. In contrast, in G551D intestinal tissues, IBMX was able to produce a small CFTR-related secretory response [means \u00b1 SE: jejunum, 1.8 \u00b1 0.9 \u03bcA\/cm<jats:sup>2<\/jats:sup>, n = 7; cecum, 3.7 \u00b1 0.8 \u03bcA\/cm<jats:sup>2<\/jats:sup>, n = 7; rectum (in vivo), 1.9 \u00b1 0.9 mV, n = 5]. This was approximately one order of magnitude less than the wild-type response to this agent and, in the cecum, was significantly greater than that seen in null mice ( cftr<jats:sup>UNC<\/jats:sup> ). In the trachea, IBMX produced a transient Cl<jats:sup>\u2212<\/jats:sup> secretory response (37.3 \u00b1 14.7 \u03bcA\/cm<jats:sup>2<\/jats:sup>, n = 6) of a magnitude similar to that seen in wild-type mice (33.7 \u00b1 4.7 \u03bcA\/cm<jats:sup>2<\/jats:sup>, n = 9). This response was also present in null mice and therefore is likely to be independent of CFTR. No effect of IBMX on Cl<jats:sup>\u2212<\/jats:sup>secretion was seen in the nasal epithelium of cftr<jats:sup>G551D<\/jats:sup> mice. We conclude that IBMX is able to induce detectable levels of CFTR-related Cl<jats:sup>\u2212<\/jats:sup> secretion in the intestinal tract but not the respiratory tract through the G551D mutant protein. <\/jats:p>","DOI":"10.1152\/ajpcell.1998.274.2.c492","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T16:35:27Z","timestamp":1514133327000},"page":"C492-C499","source":"Crossref","is-referenced-by-count":14,"title":["Effect of IBMX and alkaline phosphatase inhibitors  on Cl<sup>\u2212<\/sup> secretion in G551D cystic fibrosis mutant mice"],"prefix":"10.1152","volume":"274","author":[{"given":"Stephen N.","family":"Smith","sequence":"first","affiliation":[{"name":"Ion Transport Unit, National Heart and Lung Institute, London SW3 6LR, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Delaney","sequence":"additional","affiliation":[{"name":"Department for Molecular and Cellular Biology, University of Queensland, Brisbane 4072, Australia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia R.","family":"Dorin","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Farley","sequence":"additional","affiliation":[{"name":"Ion Transport Unit, National Heart and Lung Institute, London SW3 6LR, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan M.","family":"Geddes","sequence":"additional","affiliation":[{"name":"Ion Transport Unit, National Heart and Lung Institute, London SW3 6LR, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Porteous","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon J.","family":"Wainwright","sequence":"additional","affiliation":[{"name":"Department for Molecular and Cellular Biology, University of Queensland, Brisbane 4072, Australia; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric W. 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