Cmi. Rabergh et al., The resin acids dehydroabietic acid and isopimaric acid release calcium from intracellular stores in rainbow trout hepatocytes, AQUAT TOX, 46(1), 1999, pp. 55-65
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.