Comparative effects of loop diuretics on AVP-receptor binding and AVP-sensitive adenylate cyclase activity.
The effects of loop diuretics (azosemide, ethacrynic acid and furosemide) on arginine vasopressin (AVP) receptor-adenylate cyclase components were compared in rat renal basolateral membranes. AVP binding was inhibited by these loop diuretics at concentrations above 10(-4) M. At the IC50 of azosemide and ethacrynic acid, the Kd values were significantly increased, while the Bmax values remained unchanged. These findings indicate an inhibitory effect of loop diuretics at high concentrations on the AVP binding to its receptors. Both the basal (AVP-unstimulated) and AVP-stimulated cyclic AMP productions were also inhibited by addition of these drugs. The inhibitions of the AVP binding and AVP-sensitive adenylate cyclase activity were dose-dependent. The above findings suggest that loop diuretics, especially azosemide and ethacrynic acid, can inhibit the basal and AVP-sensitive adenylate cyclase activities directly and also indirectly via the AVP receptor, at least in part. Comparing the loop diuretics, azosemide exerts a similar effect to ethacrynic acid, and they have a more potent antagonistic effect than furosemide with respect to AVP adenylate cyclase activation.
Osajima
A
A
Second Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Anai
H
H
Segawa
K
K
Muta
T
T
Takasugi
M
M
Kuroiwa
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D017483:Receptors, Vasopressin; D013424:Sulfanilamides / Q000494:pharmacology*; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides
D000262:Adenylyl Cyclases; D004976:Ethacrynic Acid; D005665:Furosemide; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D013424:Sulfanilamides; C018222:azosemide; D013777:Tetrazoles; D013876:Thiophenes; D000096926:Benzenesulfonamides