Modulation of neuronal MAO activity, 5-HT uptake and imipramine binding by endogenous substances in dog cerebrospinal fluid

Abstract

Addition of small amounts of dog cerebrospinal fluid (CSF) inhibited both type A and type B monoamine oxidase (MAO) in dog brain mitochondria. The inhibition was competitive with 5-HT as substrate, but non-competitive with β-phenylethylamine as substrate. Tricyclic antidepressants also exhibited competitive inhibition with type A MAO, but were non-competitive with type B MAO. The endogenous materials in CSF activate [ 3H]-imipramine specific, dose-dependent binding in dog brain preparations. The maximum number of binding sites ( B max) increased, but the dissociation constant ( K d) was altered significantly in the presence of CSF. Addition of CSF induced a marked activation of uncompetitive [ 14C]-5-HT uptake in dog brain preparations. Moreover, there were reversibilities of the inhibition of MAO activity or of the activation of imiprainine binding and 5-HT uptake by CSF substance after dilution experiment. These results indicate the possible presence of an endogenous psychotic druglike substance in CSF.