Transmitter releasing action of selegiline ((—)-deprenyl) from peripheral sympathetic nerves under different experimental conditions

Abstract

Abstract A high concentration of selegiline ((—)-deprenyl; 10−4M) potentiated low frequency (2 Hz) nerve stimulation-evoked release of [3H]noradrenaline from the isolated main pulmonary artery of the rabbit in the presence of neuronal (cocaine, 3 times 10−5M) and extraneuronal (corticosterone, 5 times 10−5M) uptake blockers, and inhibited the postsynaptic response. The transmitter-releasing action of 10−4M selegiline was inhibited by a moderate increase of external K+ (23ṁ6mM). Excess K+ by itself abolished the nerve-evoked release of [3H]noradrenaline but did not increase the resting outflow of radioactivity. Excess Ca2+ (7ṁ mM) increased the stimulation-evoked transmitter release. In the presence of excess Ca2+, selegiline (10−4M) was effective in increasing the [3H]noradrenaline release in response to nerve-stimulation. Excess Ca2+ partly antagonized the postsynaptic inhibitory action of selegiline. In Ca2+-free, 1 mM EGTA-containing Krebs solution both the nerve-evoked 3H release and the transmitter releasing action of selegiline were abolished, in agreement with the ‘Ca-hypothesis’. The voltage-dependent K+-channel blocker, 4-ami-nopyridine (10−5M), increased the nerve-stimulation-evoked release of tritium from arteries. If selegiline was also present in the perfusion medium the nerve-evoked transmitter release further increased. 4-Aminopyridine completely antagonized the inhibitory action of selegiline on the postsynaptic contraction.