The effect of ethacrynic acid (EA) on the renal secretion of PAH was examined in cat kidney. CPAH and TPAH were measured before and after infusion of EA (0.5 ~ 50mg/kg) through the femoral vein. The following results were obtained: 1) In the dosage range of 0.5 to 25 mg/kg, EA increased the urine flow, and sodium and potassium excretion in dose-dependent manner, but the glomelular filtration rate was decreased as the dosage of EA was increased. 2) CPAH and TPAH were decreased by EA in the dosage range of 3 to 25 mg/kg and 1 to 50 mg/kg, respectively, in dose¡¤dependent manner with the dosage to cause 50% inhibition of about 5 mg/kg. 3) With dosage of 0.5mg/kg, EA appeared to exert a great effect on diuretic response without the influence on TPAH. At 10min after infusion of EA, a potent diuretic effect appeared, while TPAH did not show a significant change. These results suggest that the action mechanism of EA on tubular secretion of PAH may be different from that on natriuresis. 4) With dosage of 5 mg/kg, EA did not inhibit the Na-K-ATPase activity in microsomal fractions from both cortex and medulla. 5) The double reciprocal plot (l/TPAH versus l/PPAH) suggested that EA inhibited the P AH secretion by a competitive pattern. However, probenecid, a prototypic inhibitor of the organic acid pump, had no influence on both the inhibitory effect of TPAH and the natriuretic effect by EA. These results suggest that in vivo EA altered tubular secretion of P AH through interactions with receptors that are not identical with the Na-K-ATPase.
