Further study of prerequisites for the enhancement by alpha-adrenoceptor antagonists of the release of noradrenaline.

Segments of the rabbit ear artery were preincubated with (-)-3H-noradrenaline and then perfused/superfused and stimulated by transmural electrical pulses. The outflow of 3H-noradrenaline and total tritium was determined. In the first series of experiments, stimulation periods of approximately constant length (50 s) were used (cocaine 5 microM present). Thirteen pulses (0.25 Hz) elicited an overflow of 3H-noradrenaline of 0.024% of tissue tritium; 26 pulses (0.5 Hz) elicited an overflow of 0.059%, and 52 pulses (1 Hz) of 0.166%. Rauwolscine 1 microM did not change the overflow evoked by 13 pulses, increased that evoked by 26 pulses and increased most markedly that evoked by 52 pulses. Phentolamine 1 microM decreased the overflow at 13, did not change the overflow at 26, and increased the overflow at 52 pulses. Corynanthine 1 microM decreased the overflow at 13, and did not change the overflow at 26 and 52 pulses. The effect of tetraethylammonium (TEA) 100 microM was opposite to that of rauwolscine; it increased most markedly the overflow evoked by 13 pulses, increased less that evoked by 26 pulses, and least the overflow at 52 pulses. In the second series of experiments, the frequency of stimulation was kept constant (2 Hz). In the absence of cocaine, 10 pulses elicited an overflow of 3H-noradrenaline of 0.023% of tissue tritium; 20 pulses elicited an overflow of 0.043%, and 40 pulses of 0.089%. Phentolamine 1 microM did not change the overflow evoked by 10 pulses, increased that evoked by 20 pulses, and increased most markedly that evoked by 40 pulses.(ABSTRACT TRUNCATED AT 250 WORDS)