Studies on the enzymatic blood-brain barrier: quantitative measurements of DOPA decarboxylase in the wall of microvessels as related to the parenchyma in various CNS regions.
The presence of DOPA decarboxylase in cerebral microvessels (capillaries and venules) impedes the passage of circulating amine precursors into the brain. The relative amount of DOPA decarboxylase in this trapping mechanism as compared to the parenchyma per se was estimated in various CNS regions, measuring the formation of dopamine from L-DOPA in vitro or in vivo in two experimental models on rats and rabbits: (1) On the basis of the treatment with a peripheral decarboxylase inhibitor (carbidopa, which inhibits also microvascular DOPA decarboxylase in the CNS) it could be calculated that the enzyme in the microvessels of the caudate nucleus (rich in catecholamine nerve terminals), cerebellum (poor in catecholamine nerves), and spinal cord comprised 25, 91 and 79 per cent, respectively, of the total enzyme activity. (2) Measurement of dopamine formation in the spinal cord following transection at the midthoracic level (which causes degeneration of the catecholamine neurons caudal to the lesion since they are all descending) indicated that a similar fraction as found in the carbidopa model, 71%, of the total tissue decarboxylase activity resided in the microvessel walls. The results show that a considerable portion of tissue decarboxylase in the CNS is present in the microvessel walls, where it represents part of an enzymatic blood-brain barrier mechanism.
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000201:enzymology* / Q000378:metabolism; D002196:Capillaries / Q000201:enzymology; D002230:Carbidopa / Q000494:pharmacology; D002421:Caudate Nucleus / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D002531:Cerebellum / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D004296:Dopa Decarboxylase / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007980:Levodopa / Q000378:metabolism; D008833:Microcirculation / Q000201:enzymology*; D008856:Microscopy, Fluorescence; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000098:blood supply / Q000201:enzymology* / Q000378:metabolism; D014699:Venules / Q000201:enzymology
D007980:Levodopa; D004296:Dopa Decarboxylase; D002230:Carbidopa; D004298:Dopamine; D009638:Norepinephrine