ABCMdb

PMID: 15155835

Ai T, Bompadre SG, Wang X, Hu S, Li M, Hwang TC
Capsaicin potentiates wild-type and mutant cystic fibrosis transmembrane conductance regulator chloride-channel currents.
Mol Pharmacol. 2004 Jun;65(6):1415-26., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCC7 p.Gly551Asp Both capsaicin and genistein potentiate the cAMP-stimulated G551D-CFTR, ⌬F508-CFTR, and 8SA mutant channel currents. Login to comment 54 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp The 2.7-kb BspEI-PflMI fragments containing 8SA and G551D from the plasmids described above were exchanged with the corresponding ones in the pcDNA3.1 wild-type CFTR (Powe et al., 2002) to obtain the 8SA and G551D pcDNA3.1, respectively. Login to comment 62 ABCC7 p.Gly551Asp The plasmid pBudCE4.1 split ⌬R-CFTR and pcDNA3.1 constructs containing wild-type, 8SA, or G551D CFTR cDNA were cotransfected with pEGFP-C3 (BD Biosciences Clontech, Palo Alto, CA) encoding green fluorescent protein using SuperFect transfection reagent (QIAGEN, Valencia, CA) according to manufacturer`s protocols. Login to comment 142 ABCC7 p.Ser660Ala ABCC7 p.Ser737Ala ABCC7 p.Ser795Ala ABCC7 p.Ser813Ala ABCC7 p.Ser686Ala ABCC7 p.Ser768Ala ABCC7 p.Ser712Ala ABCC7 p.Ser700Ala We further explored the action of capsaicin using CFTR mutants whose eight major PKA consensus serines are substituted with alanine (S660A, S686A, S700A, S712A, S737A, S768A, S795A, and S813A), so called S-oct-A or 8SA. Login to comment 203 ABCC7 p.Gly551Asp Figure 9A shows that 100 ␮M capsaicin increased the cAMP-dependent chloride currents by ϳ6 fold in NIH 3T3 cells transiently expressing G551D-CFTR. Login to comment 205 ABCC7 p.Gly551Asp On average, the enhancement of G551D-CFTR with capsaicin was ϳ50% of that with genistein (n ϭ 6) (Fig. 9B). Login to comment 237 ABCC7 p.Gly551Asp Fifth, both compounds potentiate several different mutant CFTR channels including 8SA, G551D, ⌬F508, and ⌬R-CFTR. Login to comment 279 ABCC7 p.Gly551Asp Potentiation of G551D-CFTR and ⌬F508-CFTR by capsaicin and genistein. Login to comment 280 ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp ABCC7 p.Gly551Asp A, a whole-cell G551D-CFTR activity in the presence of various agonists. B, the I-V relationships of net G551D-CFTR-channel currents in different conditions as indicated in A. C, summary of fold increase in cAMP-stimulated G551D-CFTR activity on different agonists. Error bars represent S.E.M. **, P Ͻ 0.01 versus capsaicin. Login to comment