The response of chloride transport to cyclic AMP, calcium and hypotonic shock in normal and cystic fibrosis fibroblasts.
It has widely been established that Cl- transport is defective in cystic fibrosis fibroblasts. In the present study, the effect of elevation of intracellular concentration of cyclic AMP and calcium on the efflux of Cl- from human fibroblasts has been investigated. Cyclic AMP analogs (8-bromo cAMP and dibutyryl cAMP) and a beta agonist (isoproterenol) induced only a weak stimulation (5-10%) of Cl- efflux. Conversely, elevation of cytoplasmic calcium concentration produced by addition of the Ca2+ ionophore A23187 in the efflux medium, did not affect Cl- efflux. Our data indicate that the response of Cl- efflux to elevation of cAMP and calcium is similar in normal and cystic fibrosis fibroblasts. Exposure to hypotonic medium induced a significant stimulation of Cl- efflux in fibroblasts from both normal and cystic fibrosis individuals. Substitution of Cl- in the medium by gluconate and the subsequent addition of furosemide did not inhibit the effect of hypotonicity, indicating the involvement of a conductive pathway for Cl- transport, which was insensitive to oligomicin C.
Mastrocola
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Dip. di Biologia Evoluzionistica e Sperimentale, Università di Bologna, Italy.
Rugolo
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology; D005942:Gluconates / Q000494:pharmacology; D006801:Humans; D007038:Hypotonic Solutions / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology
D002712:Chlorides; D005942:Gluconates; D007038:Hypotonic Solutions; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D003994:Bucladesine; D005665:Furosemide; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium