PREJUNCTIONAL ALPHA-2-ADRENOCEPTORS MODULATE STIMULATION-EVOKED NOREPINEPHRINE RELEASE IN RABBIT LATERAL SAPHENOUS-VEIN

Segments of rabbit lateral saphenous vein prelabelled with [3H]noradrenaline were perfused and superfused with physiological salt solution. Tritium overflow evoked by transmural nerve stimulation (3 Hz for 2 min) was abolished by tetrodotoxin (1 .mu.M). The selective .alpha.2-adrenoceptor agonist UK 14,304 inhibited stimulation-evoked 3H-overflow in a concentration-dependent manner, with an IC50 of 71 nM. In contrast, the .alpha.2-adrenoceptor agonist B-HT 933 had no effect on 3H-overflow in concentrations up to 10 .mu.M. The selective .alpha.2-adrenoceptor antagonists idazoxan and SKF 86-466, as well as the non-selective .alpha.-antagonist phentolamine, facilitated the nerve stimulation evoked 3H-overflow, with an order of potency of idazoxan .gtoreq. phentolamine > SK and F 86466. Prazosin (100 nM) had little effect on 3H-overflow. These findings suggest that stimulation-evoked neurotransmitter release is modulated via prejunctional .alpha.2-adrenoceptors.