| Mechanism of hypocholesterolemic action of S-8921 in rats: S-8921 inhibits ileal bile acid absorption. | |
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MedLine Citation:
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PMID: 9435159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanism of the hypocholesterolemic action of S-8921, methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)- 4-hydroxy-6,7,8-trimethoxy-2-naphthoate, was examined in rats. In diet-induced hypercholesterolemic rats, 2 weeks oral administration of S-8921 dose- and time-dependently decreased plasma cholesterol level in the daily dose range of 0.1 to 10 mg/kg. Results with the dual-isotope plasma ratio method indicated that S-8921 inhibits cholesterol absorption from the intestine and enhances its elimination from the body. The in situ loop method showed that S-8921 does not inhibit the absorption of cholesterol from rat jejunum, clearly inhibits active absorption of taurocholic acid (TCA) and glycocholic acid (GCA) from rat ileum and does not inhibit passive absorption of cholic acid (CA) from the rat jejunum. In rat ileal brush-border membrane vesicles, S-8921 inhibited the sodium-dependent uptake of TCA in a concentration-dependent manner with IC50 of 2.1 microM, not the Na(+)-dependent D-glucose and L-alanine uptake. These results suggest that S-8921 is a potent, selective inhibitor of the Na(+)-dependent bile acid transport system in the ileal mucosal cell brush-border membrane, and this inhibition is the mechanism by which this drug decreases intestinal bile acid reabsorption to result in a significant decrease of plasma cholesterol. |
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Authors:
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T Ichihashi; M Izawa; K Miyata; T Mizui; K Hirano; Y Takagishi |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 284 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1998 Jan |
Date Detail:
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Created Date: 1998-02-11 Completed Date: 1998-02-11 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 43-50 Citation Subset: IM |
Affiliation:
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Formulation R & D Laboratories, Shionogi & Co., Ltd., Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticholesteremic Agents / pharmacology* Bile Acids and Salts / metabolism* Biological Transport / drug effects Ileum / metabolism* Intestinal Absorption / drug effects* Male Naphthols / pharmacology* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Bile Acids and Salts; 0/Naphthols; 151165-96-7/S 8921 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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