Hypotonicity-induced changes in anion permeability of cultured rat brain endothelial cells.
Iodide efflux, an index of anion permeability, has been monitored in cultured rat brain endothelial cells. Following hypotonicity-induced swelling, large, rapid increases in permeability occur, the extent of these increases depending on the degree of hypotonicity. Such large responses are not observed with rat aortic endothelial cells. Results of anion substitution experiments suggest that iodide efflux is via a chloride channel rather than an exchanger. The efflux increase is blocked by NPPB (100 microM) but not by DIDS or DPC at 100 microM. It is dependent on intracellular ATP but unaffected by removal of external calcium. Increasing internal calcium using A23187 does not produce a change in efflux, but depletion of calcium reduces or eliminates the response to hypotonicity. The response is reduced by pimozide (2-50 microM) that inhibits the actions of calmodulin and by pBPB (10 microM) that affects phospholipase A2 activity. It is eliminated by 5-lipoxygenase inhibitors (L-656,224 and ETH615, 10 microM) but is unaffected by cyclo-oxygenase inhibitors (indomethacin and piroxicam, 1-100 microM). It is blocked by some modulators of P-glycoprotein activity, e.g., verapamil (100 microM), tamoxifen (50 microM), and progesterone (100 microM) but not by others, e,g., forskolin (40 microM), dideoxyforskolin (40 microM), quinidine (100 microM) and cyclosporin A (10 microM).
von Weikersthal
S F
SF
Department of Pharmacology, University of Cambridge, UK.
Hickman
M E
ME
Hladky
S B
SB
Barrand
M A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000838:Anions / Q000378:metabolism; D001011:Aorta / Q000166:cytology; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D051381:Rats
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000838:Anions; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007038:Hypotonic Solutions; D007454:Iodides; D016859:Lipoxygenase Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2