AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 1 163-R171, Copyright © 1997 by American Physiological Society
Use of [3H]methylglucose and [14C]iodoantipyrine to determine kinetic parameters of glucose transport in rat brain
K. Mori and M. Maeda
Department of Neurosurgery, Juntendo University, Izunagaoka Hospital, Shizuoka, Japan.
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.
