Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters of glucose transport in rat brain.
Local maximal velocities of transport (Tmax) and the half-maximum transport constants (KT) for glucose transport across the blood-brain barrier have been determined in local regions of the brain in normal conscious rats. [14C]iodoantipyrine and [3H]methylglucose were infused together intravenously for 2 min in rats with plasma glucose concentrations maintained at different levels, and the time courses of the tracer levels in arterial blood were measured. Local 14C and 3H concentrations were then measured in tissue samples dissected from the frozen brains. By comparing the transport-limited uptake of [3H]methylglucose with the blood flow-limited uptake of [14C]iodoantipyrine, the value of m, a factor between 0 and 10 that accounts for diffusion and/or transport limitations, was derived, and from the equation, m = 1 - PS/F (where PS is capillary permeability-surface area product and F is cerebral blood flow), the permeability-capillary surface area for methylglucose was calculated (S. S. Kety. Pharmacol. Rev. 3: 1-41, 1951). Values for Tmax and KT for glucose were calculated by application of Michaelis-Menten kinetic relationships adapted for the competition for transport between glucose and methylglucose. Tmax was determined in three representative gray structures and one white structure of the brain: Tmax was 5.3 +/- 0.3 (SD) mumol.g-1.min-1 in the gray structures and 4.3 mumol.g-1.min-1 in the white structure. KT was 3.6 +/- 0.4 (SD) mM in the gray structures and 5.9 mM in the white structure. This approach allows the simultaneous determination of local values of Tmax and KT for glucose and the rates of blood flow in various regions of the brain in conscious animals.
Mori
K
K
Department of Neurosurgery, Juntendo University, Izunagaoka Hospital, Shizuoka, Japan.
Maeda
M
M
D019325:3-O-Methylglucose / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D014316:Tritium; D019325:3-O-Methylglucose; D005947:Glucose; D000983:Antipyrine; C008135:iodoantipyrine