Cloning and expression of CYP720B from Pinus brutia involved in the biosynthesis of diterpene resin acids

Abstract

The effects of two common resin acids, dehydroabietic acid (DHAA) and isopimaric acid (IPA), on potassium efflux, active potassium influx (K+/Na+-pump) and on the uptake of two bile acids (cholic acid, CHA and taurocholic acid, TCHA) were studied in hepatocytes isolated from rainbow trout, Oncorhynchus mykiss. Both resin acids inhibited the K+/Na+-pump activity at sublytic concentrations. The EC50 for the inhibition was 70μM for DHAA and 20μM for IPA. The uptake of the bile acids was inhibited at sublytic concentrations by the resin acids. The inhibition occurred at concentrations below those affecting K+/Na+ -pump. Therefore it is not likely that the inhibition of the bile acid uptake is related to the observed inhibition of the K+/Na+-pump. In view of the amphiphatic properties of the resin acids, similar to those of bile acids, it is conceivable that the resin acids could inhibit bile acid uptake by binding to the multispecific bile acid transporter or by competing for the same uptake mechanism.