Differnatial interaction of 1-methyl-4-phenylpyridinium ion with the putatively vesicular binding site of 3H-tyramine in dopaminergic and non-dopmeinergic brain regions

The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP +) in the brain striatum has recently been shown to bind at a putatively vesicular site labeled by [ 3H]tyramine ([ 3H]TY). Whereas in the rat and mouse striatum MPP + antagonized TY binding competitively, in the cerebellum there was a mixed-type antagonism, which suggests the simultaneous occupancy of two different sites. K(i) values from displacement curves revealed a fourfold difference in the affinity of MPP + for TY sites in the two brain regions. The degeneration of central noradrenergic terminals induced by an intraperitoneal injection of the toxin N-(2-chloroethyl)-N-ethyl-2- bromobenzylamine in rats decreased by 80% the maximal number of cerebellar TY binding sites, while not affecting striatal binding. Furthermore, guanethidine, a marker for noradrenaline (NA) vesicles, potently inhibited TY binding in NA-innervated regions, such as the cerebellum and the parietal cortex, and poorly in the striatum. It is concluded (a) that both MPP + and TY may also label NA vesicles and (b) that the vesicular carriers for dopamine and NA have different characteristics, which may underlie a regional specificity in the rate of endovesicular sequestration of MPP +, with either neurodegenerative or neuroprotective consequences, depending on the brain area involved.