Evidence for the involvement of alpha 1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria.

Experiments were undertaken to determine if prejunctional alpha 1-adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria. The noradrenergic transmitter stores in rat isolated atria were radiolabelled with [3H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves. Phentolamine (3 mumol/l) and prazosin (0.1 and 3 mumol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 mumol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equi-effective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin. Combination of idazoxan (10 mumol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 mumol/l). The selective alpha 1-adrenoceptor agonist methoxamine (10 mumol/l) inhibited stimulation-evoked release and this effect was blocked by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). The findings indicate that alpha 1-adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.