ABSTRACT
1,2,3,4-Tetrahydro-beta-carboline (TH beta C) is an endogenous or environmental neurotoxic factor putatively involved in the development of Parkinson's disease (PD). As part of our efforts to characterize the mechanism of the reported protection of smoking against PD, we have examined the interaction between TH beta C and cigarette smoke. We found that TH beta C reacts in vitro and under physiological conditions with some components of cigarette smoke to form N2-(cyanomethyl)-TH beta C (CM-TH beta C), N2-(gamma-cyanoethyl)-TH beta C (CE-TH beta C), N2-(1'-cyanopropyl)-TH beta C (CP-TH beta C), N2-(1'-cyanobutyl)-TH beta C (CB-TH beta C) and N2-formyl-TH beta C (F-TH beta C). Significant differences in the recovery of some of these TH beta C-derivatives were obtained for Burley and Bright tobacco. Several of the reported compounds showed reversible and competitive MAO-A inhibitory properties. The detection of some of these compounds in rat brain after chronic administration of TH beta C and a solution of cigarette smoke proved that the reported interactions also occur in vivo. These results are discussed as a potential mechanism of neuroprotection in the development of PD.
