Mechanism of L-glucose, raffinose, and inulin transport across intact blood-brain barriers.
Brain capillary permeability-surface area products (PS) of hydrophilic solutes were evaluated in terms of a conventional two-compartment model. In rats whose blood-brain barrier (BBB) was presumed to be intact, metabolically inert carbohydrates with different molecular weights were injected in pairs to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. The distribution volume of 70 kDa dextran 10 min after intravenous injection was used as a measure of the residual volume of plasma in brain tissue after death. The two-compartment model yielded larger PS values for inulin and raffinose than for L-glucose, and the PS values of inulin and L-glucose were found to decrease as the labeling time was lengthened (10, 30, and 60 min). These observations were interpreted to mean that a rapidly equilibrating compartment was present between blood and brain, rendering the two-compartment model inadequate for computing true transfer rate constants. When multiple-time uptake data were reanalyzed using the three-compartment graphical analysis of Patlak, Blasberg, and Fenstermacher (J. Cereb. Blood Flow Metab. 3: 1-7, 1983), solutes of differing molecular size were found to enter the brain at approximately equal rates. This observation suggested that the predominant transport mechanism across an intact BBB is vesicular. Specifically, unidirectional transport is likely to be initiated by solute binding to the glycocalyx on the luminal surface of brain capillary endothelium. Apparently more inulin than L-glucose is absorbed, which may account for its slightly faster transfer across the BBB. We suggest that this adsorptive surface is the location of the rapidly equilibrating compartment on the plasma side of the BBB.
Lucchesi
K J
KJ
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03756.
Gosselin
R E
RE
D000818:Animals; D001692:Biological Transport; D001696:Biomechanical Phenomena; D001808:Blood Vessels / Q000502:physiology; D001810:Blood Volume; D001812:Blood-Brain Barrier; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D005947:Glucose / Q000378:metabolism*; D007275:Injections, Intravenous; D007444:Inulin / Q000378:metabolism*; D008297:Male; D009844:Oligosaccharides / Q000378:metabolism*; D011887:Raffinose / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D009844:Oligosaccharides; D007444:Inulin; D005947:Glucose; D011887:Raffinose