The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen

Abstract

1 Twenty minutes after the addition of pargyline (5 × 10⁻⁴M) to blood perfusing the isolated spleen of the cat, the overflow of transmitter resulting from stimulation of the sympathetic nerves increased 2–3–3-fold. Lower doses of pargyline did not significantly affect overflow. 2 Monoamine oxidase activity, measured with either radioactively labelled tyramine or noradrenaline as substrate, was almost completely inhibited by doses of pargyline in the range of 10⁻⁴M to 5 × 10⁻⁴M. Inhibition of enzyme activity was not correlated with the effect on overflow. Pargyline had only a slight inhibitory effect on catechol-O-methyl transferase. 3 Uptake of a 1 μg injection (pulse) of labelled noradrenaline, following pargyline (5×10⁻⁴M), was increased to 199·1% of that found in control experiments. 4 Pargyline significantly reduced the vascular responses to nerve stimulation but had no significant effect on capsular responses. 5 The inhibitor had no effect on resting overflow of labelled noradrenaline from the spleen but doubled the overflow of labelled noradrenaline following nerve stimulation. 6 It is suggested that the effect of pargyline on overflow is due to increased release of transmitter during nerve stimulation. 7 The possible clinical significance of these findings is discussed.