Positive feedback regulation of noradrenaline release from sympathetic nerves: a questionable hypothesis

The effects of known agonists and of an antagonist on the stimulation-induced efflux of [3H]noradrenaline from left atria of guinea pigs was assessed. This was done to evaluate the hypothesis of presynaptic beta receptors mediating a positive feedback system. Isoproterenol (1.2 × 10−8 M) enhanced the efflux of tritium with 50 pulses at all four test frequencies and did so to a similar extent at three of them. Exogenous noradrenaline (1.8 × 10−6 M) inhibited efflux and isoproterenol was ineffective as an enhancer of efflux in its presence. Propranolol (1 × 10−7 M) did not reliably increase the inhibitory effect of added noradrenaline on stimulation-induced efflux nor did the antagonist by itself under a variety of test conditions decrease the stimulation-induced efflux of tritium. It is concluded that the synaptic quantities of transmitter do not determine the magnitudes of the effects of exogenous agents on tritium efflux and that positive feedback, for both theoretical and empirical considerations, does not function during neurosecretion