Combined use of [3h]methylglucose and [14c] iodoantipyrine to
determine kinetic parameters of blood-brain barrier glucose transport
in local regions of the conscious rat brain.
Mori, Kentaro, and Minoru Maeda.
Department of Neurosurgery, Juntendo University, Izunagaoka
Hospital, 1129 Nagaoka, Izunagaoka-cho, Tagata-gun, Shizuoka,
Japan
APStracts 3:0253R, 1996.
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
their 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 1.0 that
accounts for diffusion and/or transport limitations, was derived, and
from the equation, m 1 e PS/F, the permeability-capillary surface
area for methylglucose was calculated (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 and one white structure of
the brain; the mean +/- SD was 5.3 +/- 0.3 [mu]mol/g/min in the gray
structures and 4.3 [mu]mol/g/min in the one white structure. The mean
+/- SD for KT in the same structures was 3.6 +/- 0.4 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.
Received 21 February 1995; accepted in final form 20 June 1996.
APS Manuscript Number R127-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96