Differences in uptake of high-density lipoproteins by rat adrenals using in vivo vs. in situ perfusion techniques.
This study describes the effect of the delivery route of high-density lipoproteins (HDL) on the ultimate fate of the lipoprotein in the intact rat adrenal. Equal amounts of human (h)-derived affinity-purified apoE-free 125I-labeled HDL3 was given to ethinyl estradiol-treated (i.e., lipoprotein-deficient) rats either intravenously (in vivo route) or by non-recycling perfusion (in situ perfusion route). After 60-90 min, the adrenals were either excised and assessed for uptake of radioactivity, or perfusion-fixed with glutaraldehyde and prepared for autoradiograms at the electron microscope level. The results show that hHDL3 circulated in vivo binds 9-times more readily to adrenal tissues than the same quantity of ligand delivered by perfusion. Also, when the lipoprotein is administered in vivo, it is 5-times more likely to be interiorized as an intact particle by zona fasciculata (corticosterone-secreting) cells via an endocytic pathway than when delivered by perfusion. Similar differences between the in vivo and in situ routes were not seen when 125I-labeled rat HDL was the ligand delivered. Whereas the starting hHDL3 ligand was free of apoE, there was a substantial (7-fold) conversion of the HDL3 to apoE-containing HDL3 following in vivo circulation of the ligand, as shown by sodium phosphotungstate-MgCl2 precipitation or heparin-Sepharose column chromatography. These results show that the route of lipoprotein delivery to specific tissues can play a major role in determining both the binding and the processing of the ligand by the tissue in question. With hHDL3, acquisition of apoE during only 1 h of recirculation in lipoprotein-deficient rats was sufficient to totally alter the fate of the ligand in the adrenal cortex.
Azhar
S
S
Department of Medicine, Stanford University School of Medicine, Palo Alto, CA.
Reaven
E
E
D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D004997:Ethinyl Estradiol