INHIBITION BY COCAINE OF NORADRENALINE RELEASE FROM SYMPATHETIC NERVES IN THE RABBIT EAR ARTERY

1. Effects of cocaine on release of noradrenaline (NA) from sympathetic nerves were studied in the isolated perfused central artery of the rabbit ear. Indices of release were the vasoconstrictor response to nerve stimulation and stimulation-induced overflow of radioactivity after the nerves had been loaded with [3H]-NA. The overflow studies were carried out on phenoxybenzamine-treated arteries to eliminate the effect of cocaine on neuronal uptake. 2. Cocaine enhanced the constrictor responses of the artery to stimulation in concentrations of 3 and 30 mumols/l, but in higher concentrations (tested up to 300 mumols/l) the enhancement declined and was replaced by inhibition. Responses to extraluminal NA remained enhanced throughout the concentration range (tested up to 150 mumols/l). 3. In contrast, cocaine depressed the overflow of radioactivity, the effect being detectable in a concentration of 3 mumols/l (a decrease of 15%); the decrease was 40% at the highest concentration tested (90 mumols/l). 4. It is suggested that when assessed in terms of the vasoconstrictor response, inhibition of transmitter release by cocaine is masked by inhibition of neuronal uptake except in high concentrations of cocaine.