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Kinetics of Regional Blood–Brain Barrier Transport and Brain Phosphorylation of Glucose and 2‐Deoxyglucose in the Barbiturate–Anesthetized Rat
Author(s) -
Pardridge William M.,
Crane Paul D.,
Mietus Lawrence J.,
Oldendorf William H.
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb08663.x
Subject(s) - deoxyglucose , pentobarbital , chemistry , barbiturate , blood–brain barrier , glucose transporter , hypoglycemia , cerebral blood flow , phosphorylation , kinetics , endocrinology , medicine , biophysics , central nervous system , biochemistry , anesthesia , insulin , biology , physics , quantum mechanics
Recent studies indicate the lumped constant (LC), which defines the relative rates of brain utilization of glucose and 2‐deoxyglucose (2‐DG), doubles to values > 1.0 under conditions of hypoglycemia. Since changes in the LC should be predictable given the kinetic parameters of blood‐brain barrier (BBB) transport and brain phosphorylation of glucose and 2‐DG, the present studies were designed to measure the necessary kinetic parameters. The carotid injection technique was used to determine cerebral blood flow and the K m , V max , and K D of glucose and 2‐DG transport through the BBB in seven brain regions in rats anesthetized with 50 mg/kg i.p. pentobarbital. Regional glucose transport through the BBB was characterized by an average K m = 6.3 m m , average V max = 0.53 μmol min −1 g −1 , and average K D = 0.022 ml min −1 g −1 . The nonsaturable route of transport of glucose represented on the average 40% of the total glucose influx into brain regions at an arterial glucose concentration of 10 m m . In addition, the rate constants of phosphorylation of glucose and 2‐DG were measured for each region. Substitutions of the measured kinetic parameters for sugar transport and phosphorylation into equations defining the LC confirm the observation that the LC would be expected to vary under extreme conditions such as hypoglycemia and to exceed values of 1.0 under these conditions.