The effects of ethacrynic acid and furosemide on the adenylate cyclase activity of the hamster kidney and heart were examined. Ethacrynic acid and furosemide suppressed the vasopressin-mediated increment of adenylate cyclase activity much stronger than the basal activity of the renal medulla. Ethacrynic acid and furosemide strongly suppressed the parathyroid hormone-mediated increment of adenylate cyclase activity on the renal cortex, though furosemide could not inhibit the basal activity of the enzyme. Ethacrynic acid and furosemide suppressed the 1-adrenaline-mediated increment of adenylate cyclase activity of the cardiac muscle, while furosemide could not inhibit the basal activity.
Ethacrynic acid and furosemide suppressed the NaF-mediated increment of adenylate cyclase activity of the renal medulla. Thus, these diuretics seem to inhibit the catalytic unit of the enzyme. Ethacrynic acid and furosemide strongly suppressed the hormone-mediated increment of the adenylate cyclase activity, while Ca⁺⁺ could only depress it to the same degree as it did the basal activity. This difference suggests that these diuretics inhibit not only the catalytic unit of the enzyme, but also other steps of the adenylate cyclase system.
Ethacrynic acid and furosemide suppressed the effect of 5'-guanylylimido-diphosphate [Gpp (NH) p] on the adenylate cyclase activation and strongly inhibited the enzyme activity by using the combination of vasopressin and Gpp (NH) p.These results might suggest that ethacrynic acid and furosemide not only affect the catalytic unit of the adenylate cyclase, but also the GTP sensitive site of the enzyme system.