Aromatic L-amino acid decarboxylase immunoreactive cells in the rat striatum: a possible site for the conversion of exogenous L-DOPA to dopamine.
The efficacy of L-dihydroxyphenylalanine (L-DOPA) in ameliorating the symptoms of Parkinson's disease (PD) is attributed to its conversion to dopamine (DA) by the enzyme aromatic L-amino-acid decarboxylase (AADC) in the striatum. Although the site of this conversion in the DA-denervated striatum has yet to be identified, it has been proposed that L-DOPA could be converted to DA at non-dopaminergic sites containing AADC. In the present study, we used immunocytochemical techniques to examine the localization of AADC and DA in the striatum of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic projection. In the DA-denervated striatum, we observed AADC-immunoreactive (-IR) cells with morphological characteristics similar to a class of small aspiny interneuron. Although usually obscured by a dense plexus of AADC-IR fibers, these cells could also occasionally be detected in the intact striatum. Acute administration of L-DOPA to DA-denervated animals elicited contralateral rotational behavior as well as a pronounced c-fos protein immunoreactivity in the striatum ipsilateral to the lesion. Following acute administration of L-DOPA, but not after acute saline, DA-IR cells were detected in the denervated striatum. These DA-IR cells are similar in morphology and were found in the same location as the AADC-IR cells. These results strongly suggest the existence of a class of AADC-containing striatal cells that can form DA from exogenous L-DOPA in the rat. In the DA deafferented striatum, DA produced by these cells from exogenous L-DOPA could be released to exert physiological effects on DA receptive tissue. It is possible that similar cells could contribute to the efficacy of L-DOPA in the treatment of Parkinson's disease.
Mura
A
A
Department of Psychiatry, University of California San Diego, La Jolla 92093-0603, USA.
Jackson
D
D
Manley
M S
MS
Young
S J
SJ
Groves
P M
PM
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000032:analysis*; D003342:Corpus Striatum / Q000737:chemistry* / Q000166:cytology; D003714:Denervation; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007980:Levodopa / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000737:chemistry*; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D016760:Proto-Oncogene Proteins c-fos; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine