Biliary excretion of proteins in the rat during dehydrocholate choleresis

Abstract

Choleresis induced by dehydrocholate (DHC) stimulates the discharge into bile of lysosomes, which are implicated in the biliary excretion of proteins. Contrary to taurocholate-induced choleresis, DHC choleresis is not affected by microtubule (mt) inhibition. Therefore, the role of mt's in the biliary protein excretion during bile salt choleresis was analyzed in this study. Normal rats and rats treated with the mt poisons colchicine or vinblastine or with the acidotropic agent chloroquine (Cq) were used. The analysis of the protein component in bile was made on SDS–polyacrylamide gel, and the individual polypeptides were quantitated by densitometry. The excretion of bile polypeptides was compared with that of lysosomal acid phosphatase. Bile flow and bile salt output did not show changes on account of treatments. The biliary excretion of acid phosphatase was stimulated by DHC, and it was not affected by mt inhibitors but was markedly diminished by Cq. DHC choleresis produced different effects on the bile polypeptides. The biliary excretion of polypeptides of high molecular mass (84–140 kDa) was stimulated by DHC. Cq treatment increased their basal biliary excretions, whereas DHC-induced secretion was qualitatively and quantitatively similar to that of controls. The 69-kDa polypeptide (albumin) also increased during DHC-induced choleresis, but it showed a different excretory pattern. Cq treatment inhibited such an increase but no correlation with the excretory pattern of the lysosomal marker was found. The biliary excretion of polypeptides of low molecular mass (down to 14 kDa) suffered a transitory decrease and then a subsequent increase over basal values during the DHC choleresis. Cq treatment diminished their biliary excretions during basal and DHC-induced choleresis. Treatment with the mt inhibitors markedly diminished the biliary excretions of all polypeptides. The results indicate that DHC-induced choleresis influenced the biliary protein excretion in a way different to that induced by taurocholate. Thus, the biliary excretion of proteins that did not require lysosomes to reach the bile was stimulated, while that requiring such organelles was transiently diminished. In addition, the biliary excretion of proteins was dependent on mt's excepting those of lysosomal source.Key words: dehydrocholate choleresis, biliary proteins, microtubule inhibitors, chloroquine.