Effect of monoamine oxidase A and B inhibition on the uptake and metabolism of serotonin within serotonergic neurons of rat brain.

The effects of inhibiting monoamine oxidase (MAO) A and B on metabolism and uptake of serotonin (5-HT) in serotonergic synaptosomes were studied. To avoid contamination by extrasynaptosomal MAO, synaptosomes were separated from other components of rat brains by discontinuous sucrose density gradient centrifugation. Kinetic analysis of 5-HT uptake demonstrated that 5-HT was selectively transported into serotonergic synaptosomes through the high affinity 5-HT uptake process. Selectivity of the uptake and subsequent deamination of 5-HT within serotonergic synaptosomes were confirmed using selective and non-selective 5-HT and norepinephrine (NE) uptake inhibitors. MAO inhibitor analysis of 5-HT deamination occurring within serotonergic synaptosomes indicated that, at physiologically relevant concentrations of 5-HT, MAO A deaminates 5-HT, maintaining a low cytoplasmic concentration of 5-HT. When the cytoplasmic concentration of 5-HT is increased above physiologically relevant levels by the inhibition of MAO A, MAO B becomes active. [( 14)C] 5-HT uptake into synaptosomes was reduced by decreasing the V( max) of [(14)C] 5-HT uptake. One mechanism for a decrease in the V(max) could be the increase in the cytoplasmic concentration of 5-HT.