CFTR-adenylyl cyclase I association responsible for UTP activation of CFTR in well-differentiated primary human bronchial cell cultures.

ABSTRACT: Chloride secretion by airway epithelial cells is defective in cystic fibrosis (CF). The conventional paradigm is that CFTR is activated through cAMP and protein kinase A (PKA), whereas the Ca(2+)-activated chloride channel (CaCC) is activated by Ca(2+) agonists like UTP. We found that most chloride current elicited by Ca(2+) agonists in primary cultures of human bronchial epithelial cells is mediated by CFTR by a mechanism involving Ca(2+) activation of adenylyl cyclase I (AC1) and cAMP/PKA signaling. Use of selective inhibitors showed that Ca(2+) agonists produced more chloride secretion from CFTR than from CaCC. CFTR-dependent chloride secretion was reduced by PKA inhibition and was absent in CF cell cultures. Ca(2+) agonists produced cAMP elevation, which was blocked by adenylyl cyclase

SUBMITTER: Namkung W 

PROVIDER: S-EPMC2912350 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature