Effects of cyanide in vitro on the activity of monoamine oxidase in striatal tissue from rat and pig.

We have shown previously in the rat that lethal, acute cyanide intoxication dramatically decreased the levels of dopamine (DA) in the striatum, while the synthesis of DA was increased. The main brain metabolite of DA, homovanillic acid, was also diminished. However, the levels of the oxidatively deaminated metabolite of DA, 3,4-dihydroxyphenylacetic acid, were not significantly changed. In order to elucidate further these findings we examined the effects in vitro of sodium cyanide on rat and pig brain monoamine oxidase (MAO; EC 1.4.3.4). The MAO activity was measured radiochemically using [14C]5-hydroxytryptamine (5-HT; 100 microM), [14C]phenethylamine (PEA; 20 microM) and [14C]DA (100 microM) as substrates. The amounts of cyanide added were comparable to those tissue concentrations of cyanide usually considered to be fatal in rats. The effect of cyanide on MAO was immediate. In rat, as well as pig, striatal tissue we found that cyanide produced a dose-dependent increase in the activity of MAO-A (as measured with 5-HT), but not MAO-B (as measured with PEA). The change in MAO activity was also seen with DA as substrate (MAO-A and -B). Kinetic constants, Km and Vmax, were determined. In both rat and pig striatum the Vmax values for 5-HT were significantly increased, but the values for PEA were not affected. A significant decrease in the Km value for PEA was, however, found in the presence of high concentrations of cyanide.