ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
A high-affinity (Kd= 5.9 nM) specific binding site for [3H]harmaline was detected in membranes from rat and bovine brains. Studies of the regional and subcellular distributions of this binding indicated its close association with monoamine oxidase type A activity (MAO A) measured with [3H]serotonin ([3H]5-HT) as the substrate. Maximal binding capacity and MAO A activity were found in mitochondrial enriched fractions. Mitochondria of synaptosomal or extra-synaptosomal origin exhibited very similar properties with respect to [3H]harmaline binding characteristics and MAO A activity.Among psychoactive drugs, only monoamine oxidase inhibitors (MAO I) prevented the specific binding of [3H]harmaline. Logit-log inhibition curves of binding by MAO I gave only one slope which was not significantly different from 1.0, suggesting the existence of only 1 category of specific sites for [3H]harmaline in the membrane preparations from rat and bovine brains. Consistent with the preferential inhibition of MAO A by harmaline, other MAO I of this class, i.e. clorgyline and Lilly 51641, were 102-2 × 103 times more efficient than deprenyl and pargyline, two inhibitors of MAO type B, in displacing [3H]harmaline from its specific binding site. Ki and IC50 values for the inhibition of [3H]harmaline binding by MAO I and MAO substrates (tryptamine, 5-HT, norepinephrine) were almost identical with those characterizing their action on MAO A activity with [3H]5-HT as the substrate. In conclusion, the specific binding site for [3H]harmaline exhibited all the expected properties of the active site of MAO A. Like the technique of precipitation with a specific antibody, binding of [3H]harmaline should be of great help for studying the structural characteristics of the active site of MAO A and determining the number of MAO molecules in tissues under various physiological conditions.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1471-4159.1979.tb02296.x
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