Origin of various enzymes released from the substantia nigra and caudate nucleus: effects of 6-hydroxydopamine lesions of the nigro-striatal pathway.

Various enzymes are released from the nigro-striatal pathway. The hypothesis that these enzymes--i.e., acetylcholinesterase, nonspecific cholinesterase, aminopeptidase, and lactate dehydrogenase--originate from dopaminergic nigro-striatal neurons was investigated. Following a 6-hydroxydopamine lesion of the rat nigro-striatal pathway, the spontaneous release of all four enzymes was reduced, in both the caudate nucleus and substantia nigra. In both structures the reduction in release of aminopeptidase and lactate dehydrogenase was less marked than that seen for acetylcholinesterase and nonspecific cholinesterase. In nonlesioned rats, application of 50 mM KCl to the substantia nigra led to an increase in enzyme release locally, accompanied by a decrease in release from the caudate nucleus. These changes were observed in release of acetylcholinesterase, aminopeptidase, and lactate dehydrogenase, but nonspecific cholinesterase remained unchanged. In rats with 6-hydroxydopamine lesions, nigral application of potassium no longer induced a significant decrease in release from the caudate nucleus in any of the enzymes. In perfusates of the treated group, however, a potassium-evoked increase in nigral aminopeptidase and lactate dehydrogenase release was still detectable. Nigral acetylcholinesterase release was not affected by potassium in animals with 6-hydroxydopamine lesions. It appears that lactate dehydrogenase and aminopeptidase are released together from both dopamine- and non-dopamine-containing cells in the caudate nucleus and substantia nigra; this release may be related to neuronal depolarization. A high proportion of nonspecific cholinesterase is released from nigro-striatal dopamine-containing cells but appears not to be dependent on depolarization. Acetylcholinesterase, which is released in the caudate nucleus and substantia nigra following neuronal depolarization, originates almost exclusively from dopamine-containing nigro-striatal neurons.