Chloride efflux in cyclic AMP-induced configurational change of bovine pulmonary artery endothelial cells.
Elevation of cellular cyclic AMP by agents such as isoproterenol plus 3-isobutyl-1-methylxanthine produced rapid and reversible dendritic formation of bovine pulmonary artery endothelial cells in the monolayer. The effect did not occur with exposure of the cells to a variety of other vasoactive agents, calcium ionophore, phorbol ester, or cyclic GMP. The cyclic AMP-induced configurational change was completely inhibited by 2.5 mM N-phenylanthranilic acid or 145 mM sodium gluconate (Cl- channel inhibitors) and was partially inhibited by 2.5 mM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS), but it was not affected by deprivation of Ca2+ or Na+ ion, 1 mM bumetanide (Cl- cotransport inhibitor), 1 mM amiloride (Na+/H+ exchange inhibitor), 0.1 mM verapamil (Ca2+ channel inhibitor), or 5 mM BaCl2 (K+ channel inhibitor), by change in cellular pH, or by pertussis toxin. Trifluoperazine (calmodulin inhibitor, 50 microM), 1 mM EGTA plus 100 microM 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8, intracellular Ca2+ antagonist), and 5 microM cytochalasin B also produced cellular retraction, but these changes were not blocked by chloride channel inhibition. In the presence of 0.1 mM ouabain plus 0.1 mM bumetanide, 36Cl- uptake was decreased by isoproterenol plus isobutylmethylxanthine while its efflux was enhanced. N-Phenylanthranilic acid inhibited the stimulated efflux. We conclude that cyclic AMP induces a configurational change of endothelial cells that is related to Cl- efflux from the cells; the cellular effects may play a role in vascular function.
Department of Medicine, New England Medical Center Hospitals, Boston, Massachusetts 02111.
S
S
Ueda
S L
SL
Lee
B L
BL
Fanburg
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003470:Culture Media; D000242:Cyclic AMP / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007474:Ion Exchange; D008855:Microscopy, Electron, Scanning; D008858:Microscopy, Phase-Contrast; D011651:Pulmonary Artery / Q000166:cytology* / Q000378:metabolism
D002712:Chlorides; D003470:Culture Media; D007473:Ion Channels; D000242:Cyclic AMP