SINGLE PULSE STIMULATION OF GUINEA-PIG VAS-DEFERENS AND THE PRESYNAPTIC RECEPTOR HYPOTHESIS

The effect of phenoxybenzamine on the efflux of [3H]‐noradrenaline and the mechanical response to single pulse excitation of superfused guinea‐pig vas deferens was determined to examine the validity of the currently accepted hypothesis of a presynaptic negative feedback system on adrenergic nerve terminals. The adrenoceptor antagonist enhanced both the outflow of tritium and the mechanical response to single pulse stimulation. The efflux of labelled material and the responses to 4 pulses were also enhanced, as expected. Blockade of neuronal and extraneuronal uptake did not by itself increase nerve‐induced outflow or the mechanical response nor did it prevent phenoxybenzamine from doing so. The present observations cannot be accommodated within the framework of a hypothesis that proposes that the enhancement of response and tritium efflux by phenoxybenzamine results from blockade of a feedback system whereby noradrenaline released by previous impulses inhibits its own subsequent release. 1979 British Pharmacological Society