Effects of Cl- transport inhibitors on Cl- permeability across hamster ascending thin limb.
The highly conductive Cl- transport pathway exists in the ascending thin limb (ATL) of Henle's loop. To characterize the mechanism of the Cl- conductance across the ATL, we examined effects on Cl- permeability across hamster ATL of Cl- transport inhibitors, including 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), diphenylamine carboxylate (DPC), and anthracene-9-carboxylic acid (9-AC), by the in vitro microperfusion technique. NPPB added to the bath caused reversible suppression of the relative permeability of Cl- to Na+ (PCl/PNa), as estimated from the NaCl diffusion voltage in a dose-dependent manner in a range from 3 x 10(-6) to 10(-3) M. The concentration of NPPB that inhibited PCl/PNa by 50% (ID50) was approximately 3 X 10(-5) M. When 3 X 10(-5) M NPPB was added to the bath, the lumen-to-bath flux coefficient for 36Cl (Kl----b,Cl- 10(-7) cm2/s) was decreased from 130.7 +/- 7.3 to 52.2 +/- 11.6 (n = 7, P less than 0.01). Application of NPPB in the lumen also caused reversible suppression of PCl/PNa, but this effect was less potent compared with the application of the drug via the bath. Whereas 10(-3) M 9-AC or 10(-3) M DPC decreased PCl/PNa by 6.5 +/- 1.2 and 10.2 +/- 2.6%, respectively, 3 X 10(-4) M NPPB decreased PCl/PNa by 69.7 +/- 3.8%. In maleimide-treated tubules, addition of 10(-3) M N-ethylmaleimide (NEM) increased PCl/PNa from 1.0 +/- 0.1 to 1.8 +/- 0.1 (n = 7, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Isozaki
T
T
Department of Pharmacology, National Cardiovascular Center, Osaka, Japan.
Yoshitomi
K
K
Imai
M
M
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D006224:Cricetinae; D004058:Diffusion; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008647:Mesocricetus; D009579:Nitrobenzoates / Q000494:pharmacology*; D010539:Permeability
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D009579:Nitrobenzoates; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D005033:Ethylmaleimide