Use of D,L-alpha-monofluoromethyldopa to distinguish subcellular pools of aromatic amino acid decarboxylase in mouse brain.

Mice treated with D,L-alpha-monofluoromethyl-dopa (MFMD, RMI 71963), an irreversible inhibitor of aromatic L-amino acid decarboxylase (AADC), showed marked decrease in whole-brain concentrations of norepinephrine, dopamine and serotonin. The recovery of these concentrations to control values was slower than would be predicted on the basis of the activity of AADC measured in whole-brain homogenates. Subcellular fractionation of brain homogenates prepared from mice treated with MFMD showed that at least two pools of AADC activity could be distinguished by differences in their recovery rates. In the synaptosomal pool, which represents the nerve terminal AADC, the recovery of enzyme activity was significantly delayed with respect to the non-synaptosomal pool. These findings can be explained on the basis of enzyme synthesis within the nerve cell bodies and subsequent axonal transport to the nerve terminals which are the major sites of neurotransmitter synthesis.