Plasma cholesterol reducing effect of FR129169, a novel Acyl-CoA:cholesterol acyltransferase inhibitor, in the rat

Japanese Journal of Pharmacology

Volumn 70, Issue 1, 1996, Pages 35-41

  Sakuma, Yuri ^a   Hagihara, Hiroyuki ^a   Ohne, Kazuhiko ^a   Nagayoshi, Akira ^a   Mutoh, Seitaro ^a   Ito, Yoshikuni ^a   Notsu, Yoshitada ^a   Okuhara, Masakuni ^a  

^a ASTELLAS PHARMA INC   (Japan)

Author keywords

Acyl CoA:cholesterol acyltransferase; Atherosclerosis; Cholesterol absorption; FR129169; Hypercholesterolemia

Indexed keywords

2,2 DIMETHYL N (2,4,6 TRIMETHOXYPHENYL)DODECANAMIDE; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; FATTY ACID; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INTESTINE ENZYME; MICROSOME ENZYME; N (1,2 DIPHENYLETHYL) 2 OCTYLOXYPHENYLACETAMIDE; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY WEIGHT; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL DIET; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG POTENCY; DRUG STRUCTURE; ENZYME ACTIVITY; ENZYME INHIBITION; FATTY ACID BLOOD LEVEL; HYPERCHOLESTEROLEMIA; LIVER HOMOGENATE; MALE; NONHUMAN; ORAL DRUG ADMINISTRATION; RABBIT; RAT; TRIACYLGLYCEROL BLOOD LEVEL;

ACETAMIDES; ADMINISTRATION, ORAL; ANILIDES; ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL; ENZYME INHIBITORS; HYPERCHOLESTEROLEMIA; LIVER; MALE; RABBITS; RATS; RATS, SPRAGUE-DAWLEY; STEROL O-ACYLTRANSFERASE;

EID: 0030071054     PISSN: 00215198     EISSN: None     Source Type: Journal    
DOI: 10.1254/jjp.70.35     Document Type: Article

References (24)

1. Fielding CT, Renston JP and Fielding PE: Metabolism of cholesterol enriched chylomicrons. J Lipid Res 19, 705-711 (1978)
2. Erickson SK and Shrewsbury MA: Rat liver acyl-coenzyme A:cholesterol acyl transferase. J Lipid Res 21, 930-941 (1980)
3. Gillies PJ and Rathgeb KA: Regulation of Acyl-CoA:cholesterol acytransferase activity in normals atherosclerotic rabbit aortas. Exp Mol Pathol 44, 329-339 (1986)
4. Tabas I and Bcykow GC: Protein synthesis inhibition in mouse peritoneal macrophages results in increased acyl-coenzyme A:cholesterol acyltransferase activity and cholesterol ester accumulation in the presence of native low density lipoprotein. J Biol Chem 262, 12175-12181 (1987)
5. Suckling KE and Stange EF: Role of acyl-CoA:cholesterol acytransferase in cellular cholesterol metabolism. J Lipid Res 26, 647-671 (1985)
6. Krause BR, Black A, Bousley R, Essenburg A, Cornicelli J, Holmes A, Homan R, Kieft K, Sekerke C and Shaw HMK: Divergent pharmacologic activities of PD132301-2 and CL277092, urea inhibitor of acyl-CoA:cholesterol acyltransferase. J Pharmacol Exp Ther 262, 734-743 (1993)
7. Trivedi BK, Holmes A, Stoeber TL, Essenburg AD, Stanfield RL and Krause BR: Inhibitors of acyl-CoA:cholesterol acyltransferase. 4. A novel series of urea ACAT inhibitor as potential hypocholesterolemic agents. J Med Chem 29, 3300-3307 (1993)
8. Bocan TM, Mueller SB, Uhlendorf PD, Newton RS and Krause BR: Comparison of CI976, on ACAT inhibitor, and selected lipid lowering agents antiatherosclepotic activity in iliac-fomeral and thoracic aortic lesions. A chemical, morphological, and morphometric evaluation. Arterioscler Thromb 11, 1830-1843 (1991)
9. Tanaka H, Ohtsuka I, Kogushi M, Kimura T, Fujimori T, Saeki T, Hayashi K, Kobayashi H, Yamada T, Hiyoshi H and Saito I: Effect of the acyl-CoA:cholesterol acyltransferase inhibitor, E5324, on experimental atherosclerosis in rabbits. Atherosclerosis 107, 187-201 (1994)
10. Heider JG, Fears R, Levy RI, Shepherd J and Packard JR: Agents which inhibit cholesterol esterification in intestine and their potential value in the treatment of hypercholesterolemia. In Pharmacological Control of Hyperlipidemia, Edited by Fears R, pp 423-438, JR Prous Science Publishers, Barcelona (1986)
11. Krause BR, Anderson M, Bisgaier CL, Bocan T, Bouslew R, DeHart P, Essenburg A, Hamelehle K, Homan R, Kieft K, McNally W, Stanfield R and Newton RS: In vivo evidence that the lipid-regulating activity of the ACAT inhibitor CI-976 in rats is due to inhibition of both intestinal and liver ACAT. J Lipid Res 34, 279-294 (1993)
12. Heigerud PK, Saarem and Norum KR: AcylCoA:cholesterol acyltransferase in human small intestine, its activity and some properties of the enzymatic reaction. J Lipid Res 22, 271-277 (1981)
13. Gallo LL, Wadsworth JA and Vahouny GV: Normal cholesterol absorption in rats deficient in intestinal acylcoenzyme A:cholesterol acyltransferase activity. J Lipid Res 28, 381-387 (1987)
14. Bell FP, Gammill RB and St John LC: U-73482: A novel ACAT inhibitor that elevates HDL-cholesterol, lower plasma triglyceride and facilitates hepatic cholesterol mobilization in the rat. Atherosclerosis 92, 115-122 (1992)
15. Kam NTP, Albright E, Mathur SN and Field FJ: Inhibition of acylcoenzyme A:cholesterol acyltransferase activity in CaCo-2 cells results in intracellular triglyseride accumulation. J Lipid Res 30, 371-377 (1989)
16. Bennett CS and Tercyak AM: Reduced cholesterol transmucosal transport in rats with inhibited mucosal acyl CoA:cholesterol acyltransferase and normal pancreatic function. J Lipid Res 25, 148-159 (1984)
17. Tanaka M, Jingami H, Otani H, Cho M, Ueda Y, Arai H, Nagano Y, Doi T, Yokode M and Kita T: Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesterol ester contents in rabbit hepatocytes. J Biol Chem. 268, 12713-12718 (1993)
18. Dashti N: The effect of low density lipoproteins, cholesterol, and 25-hydroxycholesterol on apolipoprotein B gene expression in HepG2 cells. J Biol Chem 267, 7160-7169 (1992)
19. Jiao S, Matsuzawa Y, Matsubara K, Kudo M, Tokunaga K, Odaka H, Ikeda H, Matsuo T and Tarui S: Abnormalities of plasma lipoproteins in a new genetically obese rat with non-insulin-dependent diabetes mellitus (Wistar fatty rats). Int J Obesity 15, 487-495 (1991)
20. Jiao S, Matsuzawa Y, Matsubara K, Kihara S, Nakamura T, Tokunaga K, Kubo M and Tarui S: Increased activity of intestinal acyl-CoA:cholesterol acyltransferase in rats with streptozosin-induced diabetes and restoration by insulin supplementation. Diabetes 37, 342-346 (1988)
21. Yang LY, Kuksis A and Steiner G: Comparison of the effect of hyperinsulinemia acyl-CoA:cholesterol acyltransferase activity in the liver and intestine of the rat. Atherosclerosis 107, 25-34 (1994)
22. Maecher P, Wollheim CB, Bentzen CL and Niesor E: Importance of exogenous cholesterol in diabetic rats: effect of treatment with insulin or with an acyl-CoA:cholesterol acytransferase inhibitor. Ann Nutr Metab 37, 199-209 (1993)
23. Kojima H, Hidaka H, Matsumura K, Konaka K, Kawabata T and Shigeta Y: Clinical study of exogenous sterol absorption and post-heparin plasma diamine oxidase (DAO) activity. J Jpn Atheroscler Soc 22, 85 (1994) (Abstr in English)
24. Garg A: Lipid-Lowering therapy and macrovascular disease in diabetes mellitus. Diabetes 41, Supp 2, 111 (1992)