INTESTINAL TRANSPORT OF CALCIUM IN RAT BILIARY-CIRRHOSIS

The characteristics of intestinal calcium transport in chronic cholest asis remain largely unknown. Using an experimental model of biliary ci rrhosis in the rat, we aimed to investigate changes in calcium transpo rt at the jrjjunal and ileal levels. Two methods were used: I) uptake of Ca-45 in brush border membrane vesicles and 2) measurements of tran sepithelial fluxes of calcium in Ussing chambers. Thirty days postsurg ery, cholestatic rats presented biliary cirrhosis, with normal growth, normal daily energy, and calcium intakes, but had depressed circulati ng levels of 25-(OH)-vitamin D-2 and 1,25-(OH)-vitamin D-3. Compared w ith sham-operated controls, Ca-45 uptake ([Ca2+] = 0.03 mmol) measured in vesicles from cholestatic rats was decreased by 3-fold in the duod enojejunum, in concordance with a lower content in brush border membra ne calmodulin. Other changes in brush border membrane composition incl uded decreases in structural proteins, microvillous enzymes, and in tr iglyceride content. Transepithelial fluxes of calcium measured in the ileum ([Ca2+] = 1.2 mmol) revealed in controls a net basal secretion f lux (J(net) = -30.4 +/- 8.1 mmol . h(-1). cm(-2)) that was reduced by 3-fold (p < 0.05) in vitamin D-deficient rats (J(net) = -10.4 +/- 4.8 mmol . h(-1). cm(-2)). In response to 25-(OH)-vitamin D-2 treatment, c alcium uptake rates increased by 40% in the jejunum, whereas in the il eum, the secretion flux returned to basal control levels. Oral adminis tration of taurocholate or tauroursodeoxycholate (50 mmol) depressed a lmost completely calcium uptake capacity in the duodenojejunum. By com plexing free calcium, tauroconjugated bile acids inhibited in vitro ca lcium uptake proportionally to their concentration in the medium (0-40 mmol). Our data indicate that, in rat biliary cirrhosis, transport ca pacity of calcium in the duodenojejunum is markedly reduced in associa tion with vitamin D deficiency and alterations in brush border membran e composition.