(R)SALSOLINOL N-METHYLTRANSFERASE ACTIVITY INCREASES IN PARKINSONIAN LYMPHOCYTES

Recently, an endogenous catechol isoquinoline, ethyl-6,7-dihydroxy-1,2 ,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol], was proved to be a neurotoxin specific for dopamine neurons by in vivo and in vitro exp eriments. This N-methyl(R)salsolinol was found to increase significant ly in the cerebrospinal fluid of untreated parkinsonian patients, sugg esting its possible involvement in the pathogenesis of Parkinson's dis ease, To clarify the mechanism of the increase, the activity of enzyme s related to the metabolism of the neurotoxin was examined in lymphocy tes prepared from parkinsonian patients and controls. In patients with Parkinson's disease, the activity of a neutral N-methyltransferase, m easured by using (R)salsolinol as a substrate, was found to increase s ignificantly (100.2 +/- 81.8 pmol/min/mg of protein) in comparison wit h that in controls (18.9 +/- 15.0 pmol/min/mg of protein). The distrib ution of the activity was bimodal in the parkinsonian patients, wherea s it was singular in controls, The activity of other related enzymes, an alkaline N-methyltransferase and N-methyl(R)salsolinol oxidase, in parkinsonian lymphocytes was the same as in controls. Increase of the neutral N-methyltransferase may be an endogenous factor in the pathoge nesis of Parkinson's disease.