Renal adenylate cyclase-effects of diuretics.
The in vitro effect of various diuretics on rat kidney adenylate cyclase was investigated in crude homogenates of the cortex, the outer and inner medulla. 10-3 M furosemide inhibited adenylate cyclase by 40% in the cortex, by 16% in the outer medulla and by 43% in the inner medulla. 10-3 M ethacrynic acid inhibited adenylate cyclase activity by 65% in the cortex, 59% in the outer medulla and by 57% in the inner medulla. Amiloride produced no significant inhibition of the adenylate cyclase reaction. In the cortex, furosemide partially inhibited adenylate cyclase under basal, fluoride-stimulated and parathyroid hormone-stimulated conditions. Ethacrynic acid produced a strong inhibition of adenylate cyclase activation by F- and parathyroid hormone. In the inner medulla 10-2 M F- and 1 mU antidiuretic hormone reversed the furosemide effect on adenylate cyclase. Ethacrynic acid produced a strong inhibition of adenylate cyclase in the presence of F- and antidiuretic hormone. It is suggested that inhibition of renal adenylate cyclase might be a possible mode of action of certain diuretics.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004976:Ethacrynic Acid / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014667:Vasopressins / Q000494:pharmacology
D004232:Diuretics; D010281:Parathyroid Hormone; D014667:Vasopressins; D000584:Amiloride; D005665:Furosemide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D004976:Ethacrynic Acid