Limitations of presynaptic adrenoceptor theory: the characteristics of the effects of noradrenaline and phenoxybenzamine on stimulation-induced efflux of [3H]noradrenaline in vas deferens.

The effects of noradrenaline and phenoxybenzamine on the stimulation-induced efflux of 3H-transmitter were examined in guinea-pig vasa deferentia to assess how they conform to the expectations of presynaptic receptor theory. The vasa were stimulated transmurally with 0.5, 1.0, 3.0 and 10.0 Hz and with two different train lengths (10 and 50 pulses), in the presence of either the agonist or the antagonist. Noradrenaline (3 X 10(-7) M) depressed the stimulation-induced overflow of tritium by about 60% at each test frequency with 10 pulses and about 30% with 50 pulses, except at 0.5 Hz. Phenoxybenzamine (3 X 10(-5) M) increased the efflux of tritium to a diminishing extent with increasing frequency, with both the 10 and 50 pulses, and the effect was not sensitive to train length. The finding that the effect of phenoxybenzamine decreased with frequency and that of noradrenaline was essentially independent of frequency suggests that these compounds do not function as agonist and antagonist at a presynaptic adrenoceptor regulating transmitter output. Further, the distinctly different profiles of effect for noradrenaline and phenoxybenzamine, with frequency and train length, raises the possibility that they do not have a common mechanism or site of action in achieving their effects.