Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood-brain interface

Annals of Neurology
J E Hardebo, C Owman

Abstract

The integrity of the endothelial cell lining of the cerebrovascular bed constitutes a morphological blood-brain barrier mechanism to neurotransmitter monoamines. Circulating monoamines are prevented from entering the brain primarily at the luminal membrane of the endothelial ling. The small percentage of amines that may pass this membrane is deaminated within the endothelial cells and pericytes of brain microvessels (capillaries, venules, and small veins) and, in the case of large parenchymal and pial vessels, in the smooth muscle layers, where O-methylation also takes place. In the choroid plexus a corresponding deamination and O-methylation takes place in the epithelial cells. The presence of these enzymes constitutes a further, enzymatic, blood-brain barrier in the brain vessels for these monoamines. The monoamine precursors L-3,4-dihydroxyphenylalanine (L-dopa) and L-5-hydroxytryptophan readily pass from the luminal endothelial cell membrane but are trapped by another enzymatic barrier mechanism. Within the endothelial cells and pericytes of the microvasculature, these compounds are decarboxylated to their corresponding amines and then immediately deaminated. One clinical implication of these enzymatic barrier mechanisms is...Continue Reading

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