PRESYNAPTIC BETA-ADRENOCEPTORS IN GUINEA-PIG PAPILLARY-MUSCLE - EVIDENCE FOR ADRENALINE-MEDIATED POSITIVE FEEDBACK ON NORADRENERGIC TRANSMISSION

Guinea pig papillary muscles were preincubated in the presence of 5 x 10(-9) mol/L unlabeled noradrenaline or adrenaline then incubated with (H-3)-noradrenaline and superfused. Electrical field stimulation with 180 pulses delivered at 1 or 3 Hz was used to induce overflow of radioactivity. Comparison of the effects of preexposure of the tissue to adrenaline or noradrenaline revealed that adrenaline incubation caused an enhancement of stimulation-evoked overflow of (H-3)noradrenaline and a reduction of the effect of exogenously added isoprenaline. Furthermore, the selective beta-2-adrenoceptor antagonist ICI 118,551 (10(-7) mol/L), but not the selective beta-1-adrenoceptor antagonist ICI 89,406 (10(-7) mol/L), reduced electrically evoked overflow of (H-3)noradrenaline in tissue preincubated with adrenaline but not in tissue preincubated with noradrenaline. The overflow-reducing effect of ICI 118,551 occured at stimulation with 3 Hz but not at stimulation with 1 Hz. The present results support the hypothesis that noradrenergic transmission in guinea pig papillary muscle is facilitated via beta-2-adrenoceptors, and that adrenaline may serve as transmitter in this positive feedback mechanism after its incorporation into sympathetic nerves.