Neurocatin-induced inhibition of monoamine oxidase A in rat brain synaptosomes.
Neurocatin is a small (about 2000 Da) neuroregulator isolated from mammalian brain. Earlier it was shown that addition of nanomolar concentrations of neurocatin to synaptosomes isolated from rat brain increased levels of serotonin and decreased catabolism of serotonin to 5-hydroxyindoleacetic acid (Fernandez-Novoa L and Pastuszko A. Neurosci Lett 122: 83-86, 1991). In the present study, we report that neurocatin addition resulted in a striking inhibition of monoamine oxidase A activity. This inhibition became statistically significant at a neurocatin concentration of approximately 5 nM and was significant at all higher neurocatin concentrations. Neurocatin at approximately 50 nM inhibited monoamine oxidase A activity by about 90%. The inhibitory effect of neurocatin on monoamine oxidase required its incubation with intact synaptosomes since addition after breaking the synaptosomes by hypotonic buffer or lysis by Triton X-100 almost completely blocked the inhibitory effect. Measurements of the kinetic parameters of the enzyme in lysates prepared from synaptosomes incubated with neurocatin showed a decrease in Vmax with no change in Km for the substrate (serotonin) compared to controls. Incubation of the synaptosomes with approximately 25 nM neurocatin resulted in an 80% decrease in the Vmax of monoamine oxidase A. Evidence that neurocatin is a powerful endogenous modulator of monoamine oxidase activity is particularly intriguing. This enzyme plays a major role in catabolism of the biogenic amines and is believed to contribute to several important neurological disorders.
Fernandez-Novoa
L
L
Department of Biochemistry and Biophysics, Medical School, University of Pennsylvania, Philadelphia 19104.
Pastuszko
A
A
Wilson
D F
DF
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D009479:Neuropeptides / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D008996:Monoamine Oxidase Inhibitors; D009479:Neuropeptides; D008995:Monoamine Oxidase