Potent inhibitors of glucagon-stimulated adenylate cyclase associated with serum lipoprotein particles.
Lipoprotein fractions from some individuals have inhibitory effects on rat liver adenylate cyclase. Precipitation of the lipoprotein fractions with acetone released an inhibitory factor, which was soluble in acetone-H2O (3:1, v/v). The inhibition was greater against glucagon-stimulated activity than against basal activity. Acetone extraction increased the potency of inhibition. All three lipoprotein fractions, i.e., very low, low, and high density lipoproteins, released some inhibitory component after acetone extraction. The inhibitor was concentrated in the lipoprotein fractions, since acetone extraction of plasma did not release an inhibitor. The acetone extract from the very low density lipoprotein was the most inhibitory. This material was further purified and partially characterized. The inhibitor had a molecular mass of about 500. It was inhibitory at micromolar concentrations. The material was sufficiently hydrophobic to migrate in normal-phase thin-layer chromatography (TLC). Nuclear magnetic resonance results indicated that it was not a polar lipid. There were several different inhibitory factors that were separable by TLC. The sequestration of these inhibitors into lipoproteins reduced their effectiveness in inhibiting the action of counter-regulatory hormones, such as glucagon.
Bilan
P J
PJ
Department of Biochemistry, McMaster University, Hamilton, Ont., Canada.
Weitzman
J B
JB
Pflieger
T
T
Lancaster
C R
CR
Stafford
A
A
Epand
R M
RM
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000302:isolation & purification / Q000378:metabolism; D000818:Animals; D002850:Chromatography, Gel; D002855:Chromatography, Thin Layer; D005934:Glucagon / Q000502:physiology; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000067956:Adenylyl Cyclase Inhibitors; D008079:Lipoproteins, VLDL; D005934:Glucagon; D000262:Adenylyl Cyclases