Blood-brain barrier monoamine oxidase: enzyme characterization in cerebral microvessels and other tissues from six mammalian species, including human.
We studied the enzyme monoamine oxidase (MAO) in isolated cerebral microvessels, and in mitochondria-enriched brain and liver preparations from six mammalian species, including human. We also studied MAO distribution in various tissues and in discrete brain regions of the rat. MAO was assessed by measuring the specific binding of [3H]pargyline, an irreversible MAO inhibitor, and the rates of oxidation of known MAO substrates: benzylamine, tyramine, tryptamine, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Molecular forms of MAO were examined by using specific MAO inhibitors, and by polyacrylamide gel electrophoresis after [3H]pargyline binding. In general, the liver from all species had higher MAO levels than the brain, with minor variation among species in their brain and liver MAO content. However, there were remarkable species differences in brain microvessel MAO, with rat microvessels having one of the highest MAO activity among all tissues, whereas MAO activities in brain microvessels from humans, mice, and guinea pigs were very low. In most rat tissues, including the brain, there was a preponderance of MAO-B over MAO-A. The only exceptions were the heart and skeletal muscle. Estimates of MAO half-life in rat brain microvessels, rat brain, and rat liver indicated that microvessel MAO had a higher turnover rate. The reasons underlying the remarkable enrichment of rat cerebral microvessels with MAO-B are unknown, but it is evident that there are marked species differences in brain capillary endothelium MAO activity. The biological significance of these findings vis a vis the role of MAO as a "biochemical blood-brain barrier" that protects the brain from circulating neurotoxins and biogenic amines should be investigated.
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier; D002536:Cerebral Arteries / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology; D002550:Cerebral Veins / Q000201:enzymology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000378:metabolism*; D010293:Pargyline / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013045:Species Specificity; D013552:Swine; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D010293:Pargyline; D008995:Monoamine Oxidase; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase