Modulation of low density lipoprotein receptor activity by bile acids: differential effects of chenodeoxycholic and ursodeoxycholic acids in the hamster.
Hamsters were fed chenodeoxycholic acid (CDC), ursodeoxycholic acid, (UDC), or no bile acid. [14C]Sucrose-labeled hamster low density lipoprotein (LDL) and methylated human LDL were infused intravenously to study LDL receptor-dependent and LDL receptor-independent organ uptake, respectively, of LDL. Biliary CDC increased during both CDC and UDC treatment. The UDC enrichment of bile after UDC feeding was relatively small. Bile acid synthesis was suppressed after both bile acid treatments. Under the condition of an acute bile fistula, the hamster LDL uptake increased in the liver, heart, and adrenals in the CDC-treated animals. During an intact enterohepatic circulation, the hepatic uptake of hamster LDL, which accounted for a major portion of the total uptake, was increased after UDC treatment. The hamster LDL uptake in the colon, which represented only a small fraction of the total uptake, increased after CDC treatment. When hamster LDL was infused at increasing concentrations, its uptake was significantly higher in the UDC-treated than in the control and CDC-treated animals. The methylated human LDL uptake showed no significant changes in the different treatment groups under either experimental condition. The study shows significantly different effects of CDC and UDC on LDL receptor activity. Since these differences are expressed in spite of a similar suppression of bile acid synthesis, UDC may directly influence LDL receptor activity.
Malavolti
M
M
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.
Fromm
H
H
Ceryak
S
S
Roberts
I M
IM
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D004764:Enterohepatic Circulation; D005243:Feces / Q000032:analysis; D005704:Gallbladder / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D000418:Albumins; D001647:Bile Acids and Salts; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid