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Journal of Lipid Research, Vol 29, 144-156, Copyright © 1988 by Lipid Research, Inc.
JM Crawford, CA Berken and JL Gollan
The role of the hepatocyte microtubular system in the transport and
excretion of bile salts and biliary lipid has not been defined. In this
study the effects of microtubule inhibition on biliary excretion of
micelle- and non-micelle-forming bile salts and associated lipid were
examined in rats. Low-dose colchicine pretreatment had no effect on the
baseline excretion of biliary bile salts and phospholipid in animals
studied 1 hr after surgery (basal animals), but slightly retarded the
excretion of tracer [14C]taurocholate relative to that of
lumicolchicine-pretreated (control) rats. However, colchicine pretreatment
resulted in a marked reduction in the excretion of 2 mumol/100 g doses of a
series of four micelle-forming bile salts of differing hydrophilicity, but
had no significant effect on the excretion of the non-micelle-forming bile
salt, taurodehydrocholate. Continuous infusion of 0.2 mumol of
taurocholate/(100 g.min) following 24 hr of biliary drainage
(depleted/reinfused animals) resulted in physiologic bile flow with biliary
excretion rates of bile salts, phospholipid, and cholesterol that were
markedly inhibited (mean 33, 39, and 42%, respectively) by colchicine or
vinblastine pretreatment. Excretion of tracer [14C]taurocholate also was
markedly delayed by colchicine in these bile salt-depleted/reinfused
animals. In contrast, colchicine did not inhibit bile salt excretion in
response to reinfusion of taurodehydrocholate. Thus, under basal
conditions, the microtubular system appears to play a minor role in hepatic
transport and excretion of bile salts and biliary lipid. However, biliary
excretion of micelle-forming bile salts and associated phospholipid and
cholesterol becomes increasingly dependent on microtubular integrity as the
transcellular flux and biliary excretion of bile salts increases, in both
bile salt-depleted and basal animals. We postulate that cotransport of
micelle-forming bile salts and lipids destined for biliary excretion, via
an intracellular vesicular pathway, forms the basis for this microtubule
dependence.
ARTICLES
Role of the hepatocyte microtubular system in the excretion of bile salts and biliary lipid: implications for intracellular vesicular transport
Department of Pathology, Harvard Medical School, Boston, MA.
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