Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chlorideconductance: antagonism studies and theoretical modeling of two different receptor site interactions

The R-(+) enantiomer of 2-(p-chlorophenoxy) propionic acid (CPP) produces a biphasic effect on chloride channel conduct-ance (GCI) of rat skeletal muscle, increasing GCI at low concen-trations and decreasing It at concentrations greater than 10 tiM; on the other hand, the S-(-) isomer mostly blocks GCI in a concentration-dependent manner. To explain the peculiar behav-ior of these compounds, a theoretical model based on the presence of two opposing receptor populations controlling chlo-ride channel conductance has been used to fit the experimental data of the concentration-response curves of both S-(-) and R-(+) CPP. An analysis performed by means of the algebraic summation of two logistic terms suggests a reasonable merit of the proposed model and explains the resultant effect of each opticalform asfollows: S-(-)acts as a full agonist on an inhibftor