Human blood-brain barrier transferrin receptor.
The kinetics of binding and endocytosis of 125I-human holotransferrin by isolated human brain capillaries was examined using this system as a model of the human blood-brain barrier (BBB). Both binding and endocytosis of the peptide by human brain capillaries was temperature-dependent and the binding was saturated by holotransferrin, but not by insulin, somatostatin, or vasopressin. Scatchard analysis of the binding reaction revealed a dissociation constant of 448 +/- 110 ng/mL (5.6 +/- 1.4 nmol/L) and a maximal binding constant (Ro) of 8.0 +/- 1.5 ng/mg protein. Thus, the affinity and capacity of the BBB transferrin receptor is within the same order of magnitude as the affinity and capacity of the BBB receptors for insulin, insulinlike growth factor-I, or insulinlike growth factor-II. The human brain capillary transferrin receptor was also detected with a mouse monoclonal antibody to the receptor using the avidin/biotin/peroxidase technique. In conclusion, these studies characterize the human BBB transferrin receptor and support the hypothesis that this receptor acts as a transport system which mediates the transcytosis of transferrin-bound iron through the brain capillary endothelial cell in man.
Pardridge
W M
WM
Eisenberg
J
J
Yang
J
J
D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007444:Inulin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism*; D013696:Temperature
D011990:Receptors, Transferrin; D007444:Inulin