Effects of enantiomers of indacrinone (MK-196) on cation transport by the loop of Henle and distal tubule studied by microperfusion in vivo

MJ Field, N Fowler and GH Giebisch

We have studied the effects of the two enantiomeric forms of the diuretic agent, indacrinone (MK-196), upon transport of sodium and potassium by the loop of Henle and distal tubule, using the technique of continuous microperfusion, in vivo, of individual tubular segments in the rat kidney. In the loop of Henle, both the (+)-and (-)- enantiomers, when included in the tubular perfusion fluid at a concentration of 5 X 10(-4) M, inhibited the reabsorption of sodium and potassium, but the (-)-enantiomer was significantly more effective in this regard than the (+)-enantiomer. Although loop sodium reabsorption was incompletely blocked by either form of the drug, potassium reabsorption by the loop was on average abolished by (-)-MK-196 and was actually converted in some experiments to an appreciable net secretory flux. In the distal tubule, both enantiomers inhibited net sodium reabsorption, but neither affected the control level of potassium secretion. These experiments provide direct evidence that the natriuretic effect of this agent is due to actions on sodium transporting sites in the loop of Henle and distal tubule. Furthermore, because potassium transport was affected only in the loop, they suggest that the nature of the cellular cation transport mechanism influenced by the drug may be different at the two nephron sites studied.

Volume 230, Issue 1, pp. 62-68, 07/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics