Tissue concentrations of ethacrynic acid and inhibition of enzymes and electrophysiological responses in the cochlea

Abstract

Tissue concentrations of 14C-ethacrynic acid (EA) were determined in cochlear structures following perilymphatic perfusion. In the stria vascularis steady state levels were reached within 30 min and closely corresponded to the concentrations of the perfusion media within the range tested (5×10−4–5×10−3 M). About 55% of the label could not be washed out. In contrast to kidney cortex, there is no evidence that the stria vascularis accumulates EA above the concentrations of the perfusion media. The I50 (50% inhibition) of the endolymphatic potential (EP) with respect to EA is about 10−5 M. Much higher concentrations are required for inhibition of strial Na+K+-ATPase (I50 about 5×10−3, with preincubation 10−3 M). It is, therefore, highly unlikely that the effects of EA upon the EP are caused by interference with Na+K+-ATPase. By contrast the I50 of strial adenylate cyclase with respect to EA is the same as that of the EP (with less than 15-min preincubation). These data are consistent with the propostion that the effects of EA upon the EP are due to interference with adenylate cyclase.