Involvement of microtubules in the swelling-induced stimulation of transcellular taurocholate transport in perfused rat liver.
An increase of the hepatocellular hydratation state, induced by hypotonic exposure, amino acids or tauroursodeoxycholate, was shown to increase within minutes the Vmax of transcellular taurocholate transport and excretion into bile [Häussinger, Hallbrucker, Saha, Lang and Gerok (1992) Biochem. J. 288, 681-689]. This stimulatory effect of cell swelling on taurocholate excretion into bile is abolished in the presence of colchicine (5 microM). On the other hand, colchicine did not affect the stimulatory action of hypotonic cell swelling on 14CO2 production from [1-14C]glycine or [1-14C]glucose. Likewise, volume regulatory K+ fluxes following anisotonic exposure were not influenced in the presence of colchicine. Lumicolchicine (5 microM), a stereoisomer of colchicine without an inhibitory effect on microtubules, did not abolish the stimulation of taurocholate excretion into bile following hypo-osmotic exposure. Hypertonic cell shrinkage decreased taurocholate excretion into bile by about 35%; this effect was fully reversible upon normotonic re-exposure. With colchicine pretreatment, however, the hypertonicity-induced inhibition of taurocholate excretion was blunted and was no longer reversible upon normotonic re-exposure. The results suggest that stimulation of taurocholate excretion into bile in response to cell swelling involves a colchicine-sensitive, probably microtubule-dependent, mechanism, but not the stimulation of other cell-volume-sensitive pathways such as glycine oxidation or the pentose-phosphate shunt. It is hypothesized that the swelling-induced stimulation of taurocholate excretion into bile is due to a microtubule-dependent insertion of bile acid transporter molecules into the canalicular membrane.
Häussinger
D
D
Medizinische Universitätsklinik, Freiburg, Germany.
Saha
N
N
Hallbrucker
C
C
Lang
F
F
Gerok
W
W
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002245:Carbon Dioxide / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D008297:Male; D008870:Microtubules / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000378:metabolism*
D007038:Hypotonic Solutions; D002245:Carbon Dioxide; D013656:Taurocholic Acid; D005947:Glucose; D003078:Colchicine; D005998:Glycine