Rat brain regional uptake and decarboxylation of L-DOPA following carotid injection

Using the carotid injection technique, the regional uptake and decarboxylation of L-DOPA at the blood-brain barrier in the rat was studied. After a single intracarotid injection in the rat followed by decapitation 15 S later, the uptake of L-DOPA was measured relative to tritiated water injected simultaneously as a diffusible internal standard. Decarboxylation was investigated with an injection mixture of L-[carboxy-14C]DOPA and L-[2,3-3H]DOPA. Uptake of L-DOPA studied over the range of 15-5,076 nmol/ml appeared to be a composite of two separate mechanisms. The saturable component had a half-maximal velocity transport value, K-t, of 336 muG. A diffusional, nonsaturable component had a diffusion constant of 0.018. A regional study showed that uptake operated at approximately the same rate in the various brain areas despite marked regional variation in catecholamine concentration. The decarboxylation of L-DOPA also occurred at a similar rate in all regions. Even when L-DOPA was injected at a concentration of 3 mM, 33-51% was decarboxylated within the 15-S period. These results support the hypothesis that L-DOPA movement into the brain occures via a neutral amino acid transport mechanism common to cerebral capillaries of different regions of the brain.