Evidence for the involvement of α1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria

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Abstract
1. Experiments were undertaken to determine if prejunctional α1-adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria. 2. The noradrenergic transmitter stores in rat isolated atria were radiolabeled with [3H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves. 3. Phentolamine (3 μmol/l) and prazosin (0.1 and 3 μmol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 μmol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equieffective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin. 4. Combination of idazoxan (10 μmol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 μmol/l). 5. The selective α1-adrenoceptor agonist methoxamine (10 μmol/l) inhibited stimulation-evoked release and this effect was blocked by the α1-adrenoceptor antagonist prazosin (0.1 μmol/l). 6. The findings indicate that α1-adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.

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