EFFECT OF NEUROCATIN ON THE ACTIVITY OF MONOAMINE-OXIDASE-B IN BAT 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 n eurocatin. This inhibition became statistically significant at a neuro catin concentration of 10 ngl 200 mu l and was significant at all high er neurocatin concentrations. At 40 ng/200 mu l, neurocatin inhibited monoamine oxidase B activity by about 60%. This inhibitory effect was almost completely abolished by breaking the synaptosomal membrane by h ypotonic buffer prior to incubation with neurocatin. In addition, incu bation of the synaptosomes in calcium free medium almost completely ab olished the inhibitory effect of neurocatin On monoamine oxidase B. Th e inhibition appeared to involve covalent modification of the enzyme m ediated by a neurocatin receptor(s). Measurements of the kinetic param eters of the enzyme showed that 20 ng of neurocatin caused a statistic ally significant decrease in V-max (by 20%) with no significant change in K-M, compared to controls. Inhibition of monoamine oxidase by neur ocatin is potentially of great clinical importance because this enzyme plays a major role in catabolism of the biogenic amines and alteratio ns in its activity is believed to contribute to several neurological d isorders.