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pubmed-article:2242032pubmed:abstractTextNovel bile salts (quaternary ammonium conjugates) inhibited cholic acid binding and transport in everted ileal sacs in vitro. The cationic piperazine conjugate of lithocholic acid (di-iodide salt, compound 8, BRL 39924A) appeared most active, inhibiting binding by 29% and transport by 59% in guinea-pig ileum (200 microM). BRL 39924A also inhibited taurocholate uptake into guinea-pig ileal sacs and cholate uptake into rat ileal sacs and was selected for further study in vivo. In hyperlipidaemic rats, BRL 39924A significantly raised cholesterol 7 alpha-hydroxylase activity and decreased hepatic accumulation of exogenous cholic acid. HDL cholesterol concentration in the serum increased and the level of VLDL plus LDL cholesterol decreased. In hyperlipidaemic guinea-pigs. BRL 39924A lowered serum total cholesterol and triglyceride levels. Although metabolic changes were less than those achieved with the bile acid sequestrant, cholestyramine, the doses of BRL 39924A used were much lower (100-500 mg/kg body wt). Selective inhibition of receptor mediated bile acid uptake may be associated with local side-effects but these novel bile salts are useful pharmacological tools to examine the effects of receptor blockade on lipoprotein metabolism.lld:pubmed
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pubmed-article:2242032pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:2242032pubmed:articleTitleEffects of novel bile salts on cholesterol metabolism in rats and guinea-pigs.lld:pubmed
pubmed-article:2242032pubmed:affiliationBeecham Pharmaceuticals Research Division, Epsom, Surrey, U.K.lld:pubmed
pubmed-article:2242032pubmed:publicationTypeJournal Articlelld:pubmed
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