Loop diuretics act directly on adenylate cyclase in rat renal tubular basolateral membranes.
We have reported previously that loop diuretics, especially azosemide and ethacrynic acid, may act not only on the AVP receptor site, but also on the post-AVP receptor site in rat renal tubular basolateral membranes. The purpose of this study was to examine whether loop diuretics (furosemide, azosemide, ethacrynic acid) affect the post-AVP receptor components, using GTP-gamma S, forskolin and cholera toxin as tools acting distal to the receptor. Adenylate cyclase activity stimulated by 10(-9)M AVP was inhibited more potently by azosemide and ethacrynic acid than by furosemide at the concentration of 10(-3) M. Azosemide and ethacrynic acid at concentrations above 10(-4) M also significantly decreased the enzyme activity that was stimulated by 10(-7) M GTP-gamma S and 10(-5)M forskolin, while significant inhibition by furosemide was observed only at 10(-3)M. In addition, the inhibitory effect of these loop diuretics on cholera toxin-stimulated enzyme activity was almost similar to the results observed in AVP-, GTP-gamma S- or forskolin-stimulated the enzyme activity. From these results, we conclude that loop diuretics, especially azosemide and ethacrynic acid, directly affect adenylate cyclase in part as well as the AVP receptor site.
Osajima
A
A
Second Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu, Japan.
Mutoh
Y
Y
Kawamura
M
M
Takasugi
M
M
Kuroiwa
A
A
D000262:Adenylyl Cyclases / Q000187:drug effects*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004232:Diuretics / Q000494:pharmacology*; D007684:Kidney Tubules / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D004232:Diuretics; D000262:Adenylyl Cyclases