Kinetics of blood-brain transport of hexoses

Abstract

1. The kinetics of transport of glucose and four other hexoses through the blood-brain barrier were studied with a tritiated-water reference technique in the anesthetized rat. Brain clearance of [14-C]hexose was measured 15 s after a single injection of the hexose and 3-HOH reference into the common carotid artery. 2. Saturation of brain clearance of [14-C]hexose conformed to Michaelis-Menten kinetics. Linear transformation of the uptake data yielded the Km of carrier-mediated hexose transport: 2-deoxy-D-glucose 6 mM, D-glucose 9mM, 3-O-methyl-D-glucose and D-galactose 40 mM. A maximum transport velocity of 1.56 mumol/g per min was calculated and shown to be constant for all five hexoses. 3. The kinetics of 3-HOH and 3-0-methyl-D-[14-C]glucose efflux from brain to blood were studied with a modification of the water reference technique. An estimate of cerebral blood flow, 0.56 ml/g per min, was made from the efflux rate constant for 3-HOH, 0.61 min-1. The fractional extraction of 3-0-methyl-D-[14C]glucose uptake from blood was estimated from the efflux rate constant, 0.22 min-1, for this sugar and found to be 0.25. This value approximated the fractional extraction of 3-0-methyl-D-[14-C]glucose uptake that was determined from influx studies (0.24). These results indicated that the bidirectional movement of glucose across the blood brain barrier was symmetrical, which suggested that barrier sugar transport is equilibrative and not active. 4. Blood-brain barrier sugar transport was shown to be reversibly inhibited by phloretin, yet no modulation of transport was demonstrable after 2 or 8 days of starvation. Finally, regional analysis (olfactory bulb, caudate-putamen nucleus, thalamus-hypothalamus, and inferior-superior colliculi) demonstrated that, in addition to blood-brain barrier permeability, brain clearance of glucose was a function of cerebral blood flow.