EFFECT OF A NOVEL DIURETIC, ETHYLBENZOYL)-4(IH)-QUINOLINONE-4-OXIME-O-SULFONIC ACID, POTASSIUM-SALT (M17055) ON NA+ AND K+ TRANSPORT IN THEDISTAL NEPHRON SEGMENTS

By using an in vitro microperfusion technique, we examined whether a n ovel loop diuretic, hyl-benzoyl)-4-(IH)-quinolinone-4-oxime-o-sulfonic acid, potassium salt (M17055), a derivative of quinolinone oxime sulf onic acids, affects Na+ and K+ transport in the distal nephron segment s, including the cortical collecting duct and connecting tubule (CNT) isolated from rabbit kidneys. M17055 added to the lumen at 1 mM caused a positive deflection of transepithelial voltage (V(T)) by 2.2 +/- 0. 4 mV. The response was less than that evoked by 10 muM amiloride (8.9 +/- 0.1 mV). In the collecting duct cell of the cortical collecting du ct from normal rabbits, M17055 depolarized the basolateral membrane by 9.2 +/- 1.3 mV, whereas amiloride hyperpolarized it by 7.6 +/- 2.4 mV . In the cortical collecting duct from deoxycorticosterone acetate-tre ated rabbits, despite the fact that both agents depolarized the basola teral membrane of the collecting duct cell, amiloride consistently hyp erpolarized the apical membrane, whereas M17055 did not cause any sign ificant changes in apical membrane voltage. In the presence of 2mM Ba+ in the lumen, the apical membrane voltage deflection by M17055 was a bolished. In addition, the magnitude of the apical membrane voltage de flection caused by an abrupt increase in luminal K+ concentration from 5 to 50 mM was significantly reduced. In the CNT, both amiloride and M17055 caused a positive deflection of V(T). However, M17055 depolariz ed the basolateral membrane by 6.6 +/- 1.6 mV, whereas amiloride hyper polarized it by 4.4 +/- 1.1 mV. Voltage deflection of the CNT cell cau sed by M17055 was also abolished in the presence 2 mM Ba++ in the lume n. In the CNT segment, M17055 decreased net K+ secretion from 29.4 +/- 5.3 to 7.2 +/- 2.8 pmol mm-1 min-1, whereas amiloride decreased net K + secretion from 50.4 +/- 5.3 to 1.0 +/- 1.1 pmol mm-1 min-1. In the p resence of Ba++, the positive V(T) deflection caused by M17055 was inc reased, whereas in the presence of amiloride the orientation Of VT def lection by M17055 was reversed to negative direction. These observatio ns support the hypothesis that M17055 directly acts on the collecting duct cell and CNT cell from the lumen to inhibit both Na+ and K+ condu ctances in the apical membrane.