The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes

Two resin acids, dehydroabietic acid (DHAA) and isopimaric acid (IPA), both abundant in pulp and paper mill effluents, were studied with respect to th eir effects on intracellular calcium and their cellular uptake in rainbow t rout. Oncorhynchus mykiss, hepatocytes. In a dose-dependent manner at subly tic concentrations, both resin acids effectively released calcium from intr acellular stores, with half-maximal releases at 74 and 58 mu M for DHAA and IPA, respectively. Both resin acids caused a maximal increase of about 500 % in the basal cytosolic level of [Ca2+](i) (normal level 131 +/- 46 nM). I n saponin-permeabilized hepatocytes, the resin acids were shown to release calcium from the same stores as those released by IP3, as indicated by a la ck of effect of DHAA and IPA on calcium release after IP3 addition. Neomyci n, which has been shown to inhibit the IP3-mediated Ca2+ release from intra cellular stores, completely abolished the effect of the resin acids on calc ium release, Heparin, an IP3-receptor antagonist, reduced the DHAA- and IPA -induced calcium release by 67 and 80%, respectively. This suggests an invo lvement of the IP3-mediated pathway in the resin acid-induced intracellular calcium release. The octanol/water partition coefficient for DHAA was dete rmined to be 1.744 +/- 0.176 (log K-ow +/- S.D.). The hepatocellular uptake of H-3-DHAA was studied in order to further elucidate the transport mechan isms of the resin acids. While the uptake of H-3-DHAA was concentration dep endent, the uptake kinetics, however, did not follow classical saturation k inetics. The bile acids cholic acid and taurocholic acid were not able to e ffectively inhibit the DHAA uptake. Thus, our results show that the hepatoc ellular toxicity of resin acids involves accumulation of these compounds in hepatocytes through a complex uptake mechanism, resulting in a specific di sturbance of the normal Ca2+ signaling machinery. (C) 1999 Elsevier Science B.V. All rights reserved.