Hyperalphalipoproteinaemic activity of BRL 26314--I. Enhanced cholesterol turnover in rats.
Administration of BRL 26314 [N-(4-chlorobenzyl)-L-phenylalanine] raises circulating high-density lipoprotein (HDL) cholesterol and lowers total triglyceride levels in rats whether maintained on stock or semi-synthetic diets. HDL is also elevated by BRL 26314 in hypothyroid rats and in rats with pre-existing hyperlipidaemia where aortic total cholesterol concentration is decreased. BRL 26314 promotes the excretion of a dose of radiolabelled cholesterol as faecal sterols and bile acids, and decreases the extent of cholesterol-radiolabelling in tissue pools, particularly the aorta and adipose tissue. The increase in cholesterol and bile acid (cholic acid) turnover distinguishes BRL 26314 from a cholestatic agent such as 1-naphthyl isothiocyanate where a superficially similar change in HDL concentration disguises an impaired cholesterol transport. BRL 26314 is not a general protein inducer but part of the mechanism of action may involve enhancement of white adipose tissue lipoprotein lipase activity.
D015058:1-Naphthylisothiocyanate / Q000494:pharmacology; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002779:Cholestasis / Q000097:blood / Q000139:chemically induced; D002784:Cholesterol / Q000097:blood*; D005243:Feces / Q000032:analysis; D006951:Hyperlipoproteinemias / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D008075:Lipoproteins, HDL; D010649:Phenylalanine; D015058:1-Naphthylisothiocyanate; C040508:BRL 26314; D002784:Cholesterol; D010634:Phenobarbital