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 intoxic ation dramatically decreased the levels of dopamine (DA) in the striat um, 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-dihydroxyphenylaceti c acid, were not significantly changed. In order to elucidate further these findings we examined the effects in vitro of sodium cyanide on r at and pig brain monoamine oxidase (MAO; EC 1.4.3.4). The MAO activity was measured radiochemically using [C-14]S-hydroxytryptamine (5-HT; 1 00 mu M), [C-14]phenethylamine (PEA; 20 mu M) and [C-14]DA (100 mu M) as substrates. The amounts of cyanide added were comparable to those t issue 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 increa se 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, K-m and V-max, were de termined. In both rat and pig striatum the V-max values for 5-HT were significantly increased, but the values for PEA were not affected. A s ignificant decrease in the K-m value for PEA was, however, found in th e presence of high concentrations of cyanide.