title: Regulation of intracellular Ca(2+) by CFTR in Chinese hamster ovary cells.
abstract: In cystic fibrosis, the mutation of the CFTR protein causes reduced transepithelial Cl(-) secretion. As recently proposed, beside its role of Cl(-) channel, CFTR may regulate the activity of other channels such as a Ca(2+)-activated Cl(-) channel. Using a calcium imaging system, we show, in adenovirus-CFTR infected Chinese Hamster Ovary (CHO) cell monolayers, that CFTR can act as a regulator of intracellular [Ca(2+)](i) ([Ca(2+)](i)), involving purino-receptors. Apical exposure to ATP or UTP produced an increase in ([Ca(2+)](i) in noninfected CHO cell monolayers (CHO-WT), in CHO monolayers infected with an adenovirus-CFTR (CHO-CFTR) or infected with an adenovirus-LacZ (CHO-LacZ). The transient [Ca(2+)](i) increase produced by ATP or UTP could be mimicked by activation of CFTR with forskolin (20 microm) in CHO-CFTR confluent monolayers. However, forskolin had no significant effect on [Ca(2+)](i) in noninfected CHO-WT or in CHO-LacZ cells. Pretreatment with purino-receptor antagonists such as suramin (100 microm) or reactive blue-2. (100 microm), and with hexokinase (0.28 U/mg) inhibited the [Ca(2+)](i) response to forskolin in CHO-CFTR infected cells. Taken together, our experiments provide evidence for purino-receptor activation by ATP released from the cell and regulation of [Ca(2+)](i) by CFTR in CHO epithelial cell membranes.
authors.affiliation: Wellcome Trust Cellular Physiology Research Unit, Department of Physiology, University College, Cork, Ireland.
authors.forename: V
authors.initials: V
authors.lastname: Urbach
authors.forename: B J
authors.initials: BJ
authors.lastname: Harvey
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology; D011983:Receptors, Purinergic / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D011983:Receptors, Purinergic; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D002118:Calcium