Neurotransmitter release in an arterial preparation and the action of alpha-adrenoceptor antagonists.

1 This study examined the potentiating effects of competitive antagonists of the adrenergic alpha2 receptors and of phenoxybenzamine (POB) an irreversible antagonist, on the stimulation-induced efflux of [3H]-noradrenaline in arterial tissue of rabbit. This was done to determine if the lack of concordance of efflux potentiation by antagonists with the expectations of presynaptic negative feedback theory can be attributed to increasingly successful competition from rising perineuronal transmitter concentrations, when stimulation parameters are increased, in the presence of a fixed concentration of competitive antagonist. 2 Tissues were stimulated with a fixed pulse number and frequency, to rule out confounding factors, and major alterations in the concentration of released transmitter were achieved through variations in the pulse duration. 3 Rauwolscine potentiated transmitter release less at the longest, rather than at the shortest pulse duration, and showed a potentiation of release that was indifferent to the quantities of released transmitter. This was also seen with POB although it binds covalently to the presynaptic receptor. 4 Noradrenaline inhibited stimulation-induced transmitter release confirming the presence of presynaptic alpha inhibitory sites. 5 Yohimbine potentiated transmitter release the same as did rauwolscine and POB, and protected the relevant sites against POB potentiation, confirming site identity. The combination of POB and rauwolscine had no greater effect than did either alone certifying that they acted similarly and that maximally effective concentrations of each were used. 6 Consequently, noradrenaline breakthrough of presynaptic receptor blockade does not explain the non-conforming observations made with competitive antagonists in tests of presynaptic theory.