| First Author | Steagall WK | Year | 1999 |
| Journal | Gastroenterology | Volume | 116 |
| Issue | 6 | Pages | 1379-88 |
| PubMed ID | 10348821 | Mgi Jnum | J:55783 |
| Mgi Id | MGI:1339402 | Doi | 10.1016/s0016-5085(99)70502-0 |
| Citation | Steagall WK, et al. (1999) Stimulation of cystic fibrosis transmembrane conductance regulator-dependent short-circuit currents across DeltaF508 murine intestines. Gastroenterology 116(6):1379-88 |
| abstractText | Background & Aims: The cystic fibrosis transmembrane conductance regulator (CFTR) can be activated by pharmacological manipulation of the protein kinase A pathway in cell lines. Our goals were to stimulate wild- type CFTR in murine intestines via isoform-specific phosphodiesterase inhibition or protein kinase A activation and to apply the optimal stimulus to activate chloride secretion from homozygous Delta F508 jejunum, Methods: The response of T84 cells and sections of murine intestine to various inhibitors and activators was examined by Ussing chamber experiments. Results: Maximal chloride secretion can be activated in T84 cells with application of class III phosphodiesterase inhibitors and in wild-type murine intestines with class I or III phosphodiesterase inhibitors or with activators of type II protein kinase A. Chloride secretion can be stimulated from homozygous Delta F508 murine jejunum using a mixture of inhibitors and activators. Conclusions: Delta F508 CFTR can be activated to levels 4% of wild-type when the combination of protein kinase A type II activators and phosphodiesterase class I and III inhibitors are used in murine jejunum, This result suggests that partial CFTR- mediated electrolyte transport can be restored in Delta F508 murine jejunum by application of specific pharmacological agents. |
