Selective modulation of noradrenaline release by α 2 ‐adrenoceptor blockade in the rat‐tail artery in vitro

The effects of blocking α 2 ‐adrenoceptors on noradrenaline (NA) and adenosine 5′‐triphosphate (ATP) release from postganglionic sympathetic nerves have been investigated in rat‐tail artery in vitro . Continuous amperometry was used to measure NA release and intracellularly recorded excitatory junction potentials (e.j.p.'s) were used to measure ATP release. Application of the α 2 ‐adrenoceptor antagonist, idazoxan (1 μ M ), increased the amplitude of NA‐induced oxidation currents evoked by trains of 10 stimuli at 1 and 10 Hz. In cells deep in the media, idazoxan (1 μ M ) had no effect on the amplitude of e.j.p.'s evoked by trains of 10 stimuli at 1 and 10 Hz. In cells close to the adventitial – medial border, idazoxan produced a small increase in the amplitude of e.j.p.'s evoked at the end of trains of 10 stimuli at 1 Hz. In tissues pretreated with the neuronal NA uptake inhibitor, desmethylimpramine (0.3 μ M ), idazoxan (1 μ M ) markedly increased the amplitude of e.j.p.'s in cells deep in the media. The α 2 ‐adrenoceptor agonist, clonidine (0.5 μ M ), produced similar reductions in the amplitudes of both NA‐induced oxidation currents and e.j.p.'s evoked by 10 stimuli at 1 Hz. These effects of clonidine were reversed by the subsequent addition of idazoxan (1 μ M ). The release of both NA and ATP is inhibited to a similar extent by activation of prejunctional α 2 ‐adrenoceptors by clonidine. In contrast, endogenously released NA more markedly inhibits NA release. These findings provide further support for the differential modulation of NA and ATP release.British Journal of Pharmacology (2004) 142 , 267–274. doi: 10.1038/sj.bjp.0705779