Research Triangle Institute, Research Triangle Park, NC 27709, U.S.A.
TRANSPORT OF SUGARS INTO MICROVESSELS ISOLATED FROM RAT BRAIN: A MODEL FOR THE BLOOD-BRAIN BARRIER1
Article first published online: 5 OCT 2006
Journal of Neurochemistry
Volume 33, Issue 2, pages 419–431, August 1979
How to Cite
Kolber, A. R., Bagnell, C. R., Krigman, M. R., Hayward, J. and Morell, P. (1979), TRANSPORT OF SUGARS INTO MICROVESSELS ISOLATED FROM RAT BRAIN: A MODEL FOR THE BLOOD-BRAIN BARRIER. Journal of Neurochemistry, 33: 419–431. doi: 10.1111/j.1471-4159.1979.tb05171.x
Presented in part at the 7th Annual Meeting of the Society for Neuroscience.
- Issue published online: 5 OCT 2006
- Article first published online: 5 OCT 2006
- (Received 26 February 1979. Accepted 7 March 1979)
Abstract— Microvessels (primarily capillaries) were isolated from the brains of rats 25-35 days of age. This preparation was characterized by light, transmission, and scanning electron microscopy. Transmission electron microscopy revealed that the endothelial cell membranes were intact and were impermeable to horseradish peroxidase. However, scanning electron microscopy revealed that damage to the membrane occurred during isolation. The isolated microvessel preparations were metabolically competent as demonstrated by their ability to metabolize [14C]glucose.
Aliquots of microvessel preparation were incubated with radioactive non-metabolizable analogs of D-glucose at various concentrations. The kinetics of accumulation of radioactivity in the capillaries were analyzed according to a model for carrier-mediated diffusion and affinity constants for 3-O-methyl- D-glucose and 2-deoxyglucose were calculated (about 18 mM at 20°C in each case). These affinity constants are somewhat greater than that expected from whole animal experiments reported by other laboratories. This discrepancy is probably accounted for by the presence of a passive diffusion component. However, despite this complication, the primary mechanism for entry of D-glucose analogues at physiological concentrations is compatible with carrier-mediated transport since: the uptake of sugar analogs was shown to be saturable, to exhibit competition for uptake between structurally similar molecules, and to be non-concentrative. In contrast, the uptake of glycerol, mannitol, and L-glucose by isolated microvessels obeyed the kinetics of simple passive diffusion and was not saturable.
Our results are compatible with the concept that the capillary is the anatomic locus of the blood-brain barrier and that this structure contains the carrier-mediated transport system for monosaccharide penetration into brain.