Differential interaction of 1-methyl-4-phenylpyridinium ion with the putatively vesicular binding site of [3H]tyramine in dopaminergic and nondopaminergic brain regions.

Abstract:

: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.

journal_name

J Neurochem

authors

Vaccari A,Saba PL,Gessa GL,Del Zompo M

doi

10.1111/j.1471-4159.1993.tb03212.x

subject

Has Abstract

pub_date

1993-02-01 00:00:00

pages

758-60

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

60

pub_type

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