Differential interaction of 1-methyl-4-phenylpyridinium ion with the putatively vesicular binding site of [3H]tyramine in dopaminergic and nondopaminergic 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. Ki 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.
Vaccari
A
A
Department of Neuroscience, Neurotoxicology Center, Cagliari, Italy.
Saba
P L
PL
Gessa
G L
GL
Del Zompo
M
M
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006145:Guanethidine / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014439:Tyramine / Q000378:metabolism*
D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D014439:Tyramine; D006145:Guanethidine