Selective modulation of noradrenaline release by alpha 2-adrenoceptor blockade in the rat-tail artery in vitro.
The effects of blocking alpha(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 alpha(2)-adrenoceptor antagonist, idazoxan (1 microm), 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 microm) 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 microm), idazoxan (1 microm) markedly increased the amplitude of e.j.p.'s in cells deep in the media. The alpha(2)-adrenoceptor agonist, clonidine (0.5 microm), 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 microm). The release of both NA and ATP is inhibited to a similar extent by activation of prejunctional alpha(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.
Brock
James A
JA
Prince of Wales Medical Research Institute, University of New South Wales, Barker Street, Randwick NSW 2031, Australia. j.brock@unsw.edu.au
Tan
Joy H C
JH
D018674:Adrenergic Antagonists / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013623:Tail / Q000098:blood supply*
D018674:Adrenergic Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D003000:Clonidine; D009638:Norepinephrine