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, 8 (1), 1-31

Barrier Mechanisms for Neurotransmitter Monoamines and Their Precursors at the Blood-Brain Interface

Barrier Mechanisms for Neurotransmitter Monoamines and Their Precursors at the Blood-Brain Interface

J E Hardebo et al. Ann Neurol.

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 the use of decarboxylase and monoamine oxidase inhibitors as adjuncts to L-dopa treatment of Parkinson disease; these substances facilitate the entry of L-dopa into brain and thus increase the amount of dopamine available at receptor sites. A brief hypertensive or hypertonic stimulus can transiently open the blood-brain barrier through an effect on endothelial cell linings. High circulating concentrations of monoamines can also open the morphological barrier, but probably only indirectly by inducing an acute rise in systemic blood pressure. Once the barrier is open, systemically administered monoamines enter the brain parenchyma, where they can induce pronounced changes in cerebral blood flow and metabolism.

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