Evidence for autoinhibition of stimulation-induced noradrenaline release from vasa deferentia of the guinea-pig and rat.

Both phenoxybenzamine and idazoxan increased the efflux of radioactivity elicited by a train of stimulation (4 pulses at 5 Hz) in vasa deferentia preincubated with [3H]-noradrenaline. Phenoxybenzamine increased the release of radioactivity from vasa stimulated with a single pulse, whereas idazoxan did not. The contractile response in both guinea-pig and rat vasa was biphasic: phenoxybenzamine enhanced the initial twitch component and reduced the second component in guinea-pig vasa stimulated with a single pulse or a train of pulses. Idazoxan enhanced both phases of the response of guinea-pig vasa stimulated with a train of pulses but did not affect the response to stimulation with a single pulse. The effect of phenoxybenzamine in increasing the efflux of radioactivity produced by a single pulse of stimulation was abolished by cocaine, indicating that the increase in efflux was due to blockade of noradrenaline uptake. Contractile responses of guinea-pig vasa stimulated with a single pulse in the presence of cocaine were unaltered by phenoxybenzamine, whereas with a train of stimulation the twitch component was enhanced and the second phase was reduced. The effects of phenoxybenzamine or idazoxan on the efflux of radioactivity from rat vasa portions were qualitatively the same as were observed in whole vasa. The contractile response of the prostatic portion consisted of a rapid twitch with a single pulse of stimulation, but was biphasic with a train of stimulation; the response of the epididymal portion was biphasic with either a single pulse or a train of pulses. These results suggest that there is no inhibitory feedback modulation of noradrenaline release with a single pulse of stimulation in guinea-pig and rat vasa deferentia whereas, with a train of stimulation, there is autoinhibition of noradrenaline release.