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  • Title: Mechanism of inhibition of hepatic bile acid uptake by amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS).
    Author: Anwer MS, Branson AU, Atkinson JM.
    Journal: Biochem Pharmacol; 1991 Dec 11; 42 Suppl():S135-41. PubMed ID: 1768270.
    Abstract:
    The mechanisms by which amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibit hepatic uptake of cholate and taurocholate (TC) were investigated in isolated rat hepatocytes. Amiloride inhibited Na(+)-dependent uptake of cholate and TC only when hepatocytes were preincubated with amiloride, indicating an indirect effect of amiloride. Time-dependent studies showed that the inhibition of bile acid uptake was associated with a parallel increase in intracellular Na+ concentration ([Na+]i). Although amiloride decreased intracellular pH, this decrease preceded amiloride-induced inhibition of bile acid uptake and increase in [Na+]i. Amiloride inhibited bile acid uptake, decreased membrane potential, and increased [Na+]i with comparable concentration dependency. DIDS inhibited Na(+)-dependent uptake of cholate and TC non-competitively. Neither DIDS nor amiloride inhibited Na(+)-independent uptake of cholate and TC. These results indicate that amiloride inhibits Na(+)-dependent cholate and TC uptake by decreasing the transmembrane Na(+)-gradient, and further support the hypothesis that two different transporters may be involved in hepatic bile acid uptake by Na(+)-dependent and Na(+)-independent mechanisms.
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