The kinetic behaviour of [3H]DOPA in living rat brain investigated by compartmental modelling of static autoradiograms

被引:14
作者
Deep, P
Kuwabara, H
Gjedde, A
Cumming, P
机构
[1] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada
[2] W Virginia Univ, Dept Neurosurg, Morgantown, WV 26506 USA
[3] Aarhus Univ Hosp, PET Ctr, DK-8000 Aarhus, Denmark
基金
英国医学研究理事会;
关键词
blood-brain clearance; chromatographic fractionation; compartmental model; DOPA decarboxylase activity; (3)H]DOPA autoradiography; (3)H]dopamine; kinetic constants; rat brain;
D O I
10.1016/S0165-0270(97)00147-7
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The kinetic behaviour of [(3)H]DOPA in living rat brain was investigated by compartmental modelling of measured activities from combined metabolite pools in a time-series (180 min) of static autoradiograms from right cerebral hemispheres. Two models of [(3)H]DOPA uptake and metabolism that incorporated the removal of the decarboxylation product, [(3)H]dopamine, from brain were significantly more accurate than a model in which [3H]dopamine accumulated irreversibly in situ. Present estimates of [(3)H]DOPA kinetic constants were compared to previously published results based on the analysis of measured activities from individual metabolite pools separated by chromatographic fractionation of [(3)H]DOPA metabolites in the left cerebral hemispheres of the same rats. Autoradiographic estimates of DOPA decarboxylase activity with respect to [(3)H]DOPA in brain (k(3)(DOPA)) were under-estimated several-fold relative to chromatographic estimates; this discrepancy is explained by post-mortem enzyme activity and omission of biological compartments from the models. However, autoradiographic estimates of the unidirectional blood-brain clearance of [(3)H]DOPA (K(1)(DOPA)) and monoamine oxidase activity with respect to [(3)H]dopamine in brain (k(7)(DA)) agreed with chromatographic estimates. This concordance represents the first empirical validation of compartmental modelling of autoradiographic data as a method for quantitatively investigating the kinetic behaviour of radiolabelled L-DOPA in living mammalian brain. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:157 / 168
页数:12
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