Effect of neurocatin on the activity of monoamine oxidase B in rat brain synaptosomes.
Neurocatin, a small (about 2,000 Dalton) neuroregulator isolated from mammalian brain, is a powerful effector of monoamine oxidase B in rat brain synaptosomes. Incubation of intact synaptosomes with neurocatin caused an inhibition of the enzyme dependent on the concentration of neurocatin. This inhibition became statistically significant at a neurocatin concentration of 10 ng/200 microliters and was significant at all higher neurocatin concentrations. At 40 ng/200 microliters, neurocatin inhibited monoamine oxidase B activity by about 60%. This inhibitory effect was almost completely abolished by breaking the synaptosomal membrane by hypotonic buffer prior to incubation with neurocatin. In addition, incubation of the synaptosomes in calcium free medium almost completely abolished the inhibitory effect of neurocatin on monoamine oxidase B. The inhibition appeared to involve covalent modification of the enzyme mediated by a neurocatin receptor(s). Measurements of the kinetic parameters of the enzyme showed that 20 ng of neurocatin caused a statistically significant decrease in Vmax (by 20%) with no significant change in KM, compared to controls. Inhibition of monoamine oxidase by neurocatin is potentially of great clinical importance because this enzyme plays a major role in catabolism of the biogenic amines and alterations in its activity is believed to contribute to several neurological disorders.
Murphy
S
S
Department of Biochemistry and Biophysics, Medical School, University of Pennsylvania, Philadelphia 19104.
Pastuszko
A
A
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D001685:Biological Factors; D009419:Nerve Tissue Proteins; C080290:neurocatin; D008995:Monoamine Oxidase