Hepatic low density lipoprotein receptors, HMG-CoA reductase, and plasma lipids and apolipoproteins in high- and low-responding rhesus monkeys: effect of cholestyramine treatment.
Plasma lipids and apolipoproteins, and hepatic LDL receptor and HMG-CoA reductase activities in biopsy samples were measured in high- and low-responding rhesus monkeys maintained on a cholesterol-rich and regular diets. The effect of a 30-day cholestyramine treatment on the above parameters under both dietary conditions was also determined. On the cholesterol-rich diet the high-responders, when compared to the low-responders, had several-fold increased plasma cholesterol and apoB concentrations and significantly lower HDL apoA-I and cholesterol concentrations. Hepatic LDL receptor and HMG-CoA reductase activities were not detectable in the high-responders, while the low-responders expressed a reduced number of LDL receptors of normal affinity. Administration of cholestyramine resulted in a rapid induction of the hepatic LDL receptors in the high-responders and a small additional increase in the low-responders. Cholestyramine treatment also stimulated the expression of the hepatic HMG-CoA reductase in both groups of monkeys. These changes were accompanied by a dramatic drop in plasma cholesterol and apoB concentrations in the high-responders and, to a lesser extent, in the low-responders. Plasma HDL concentrations in the high-responders rose to levels higher than those seen in the low-responders. The affinity and receptor number were similar in both groups of monkeys on the control diet, but the low-responders had significantly higher HMG-CoA reductase activities. Administration of cholestyramine during the control diet had a small but significant additional effect on the hepatic LDL receptors of the low-responders but not of the high-responders.(ABSTRACT TRUNCATED AT 250 WORDS)
Dory
L
L
Department of Pharmacology, University of Tennessee, Memphis 38163.
Bhattacharyya
A
A
Strong
J
J
Chappuis
C
C
D000818:Animals; D001053:Apolipoproteins / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism
D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D008055:Lipids; D011973:Receptors, LDL; D002792:Cholestyramine Resin; D006903:Hydroxymethylglutaryl CoA Reductases