Similar distribution of monoamine oxidase (MAO) and parkinsonian toxin (MPTP) binding sites in human brain

Abstract

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) causes parkinsonism in humans and other species. We found [3H] MPTP binding sites that were saturable, specific, and of high affinity. In autoradiographic studies, the highest binding densities of [3H] MPTP occurred in the hypothalamus, interpeduncular nucleus, and ependymal lining of the ventricles. High to moderate binding was seen in the dentate gyrus, caudate, putamen, substantia nigra, and cingulate cortex. The distribution of [3H] MPTP binding correlated with the distribution of [3H] pargyline binding to MAO. Human substantia nigra contains more MPTP binding sites than rat substantia nigra, and this may explain the sensitivity of humans to the neurotoxic effects of MPTP.

[3H]Tryptamine Binding Sites Are Not Identical to Monoamine Oxidase in Rat Brain

“…3. The distributions of the latter two ligands appeared to be almost identical in these and other sections, as has been reported previously Reznikoff et al, 1985). However, the distribution of [3H]tryptamine binding showed several distinct differences from the MA0 ligands.…”

“…Examination of previous autoradiographic distributions for [3H]tryptamine (Altar et al, 1986;Kaulen et al, 1986;McCormack et al, 1986;Perry, 1986), [3H]MPTP (Javitch et al, 1984;Rainbow et al, 1985;Reznikoff et al, 1985), and [3H]pargyline Reznikoff et al, 1985) revealed several major similarities. Thus, we felt that comparison of the binding of the three radioligands in serial sections of rat brain would clarify this situation.…”

“…[3H]MPTP binding utilized a radioligand concentration of 2.5-3.6 nM for competition curves; incubations were for 90 rnin on ice (Javitch et al, 1984;Parsons and Rainbow, 1984), and nonspecific binding was defined with 2 N M P T P . [3H]Pargyline binding utilized a radioligand concentration of 3.6 nM; incubation was for 30 min at room temperature Reznikoff et al, 1985), and nonspecific binding was defined with 10 pM pargyline. Competition curves were analyzed using a nonlinear curve fitting program to calculate KI values (McPherson, 1983).…”

“…Many compounds that are potent inhibitors of [3H]tryptamine binding are either MA0 substrates (kynuramine, phenylethylamine, tetrahydro-P-carboline) or inhibitors (e.g., harmaline). To test whether [3H]tryptamine is actually binding to membrane-bound MAO, we compared the binding of I3H]tryptarnine to that of [3H]pargyline and [3H] 1-methyl4phenyl-1,2,5,6-tetrahydropyridine ( in rat brain (Javitch et al, 1984(Javitch et al, , 1985; Parsons and Rainbow, 1984; Rainbow et al, 1985; Reznikoff et al, 1985). If [3H]tryptamine binding in brain represents binding to the recognition site of MAO, one would predict a close congruence of its binding behavior with that of these two radioligands (Martino-Barrows et al, 1987;Perry et al, 1988).…”

Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19- 6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain

“…The amounts of MAO-A and MAO-B, determined (in saturation experiments) by the capacity of tissues to bind 3H-Ro 41-1049 and )H-Ro 19-6327, respectively, were of the same order of magnitude as the values derived by titration of MAO-A and MAO-B with clorgyline and L-deprenyl (Fowler et al, 1980) and by binding to homogenates (Cesura et al, 1989(Cesura et al, , 1990) and tissue sections (Reznikoff et al, 1985). The Journal of Neuroscience, May 1992May , 12(5) 1993 Quantitative enzyme radioautography: distribution and abundance of MAO-A and MAO-B in rat tissues…”