Adenosine receptors involved in modulation of noradrenaline release in isolated rat tail artery

Adenosine receptors involved in the modulation of noradrenaline release from postganglionic sympathetic nerves in rat tail artery were characterized by studying the effects of adenosine-receptor agonists and antagonists on electrically evoked tritium overflow (100 pulses, 5 Hz) and by immunohistochemistry. The adenosine A, receptor-selective agonist N-6-cyclopentyladenosine (CPA; 1-100 nM) and the nonselective adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA; 1-10 muM) decreased tritium overflow. These effects were blocked by the adenosine A, receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 30 nM). The adenosine A(2A) receptor-selective agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxdmido adenosine (CGS 21680; 1-100 nM) enhanced tritium overflow, an effect blocked by the adenosine A2A receptor-selective antagonist 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261; 20 nM) but not changed by the adenosine A(2B) receptor-seiective antagonist N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,,6-dioxo-1,3-dipropyl-1H-pufin-8-yl) phenoxy]acetamide (MRS 1706; 20 nM). In the presence of DPCPX (30 nM), NECA enhanced tritium overflow, an effect abolished by MRS 1706 but not influenced by SCH 58261. Imnumohistochemistry revealed immunoreactivity for all adenosine-receptor subtypes. Areas of co-localization were found for neurofilament with adenosine A(1), A(2A) and A(2B) but not A(3) receptors. In conclusion, the present study provides functional and morphological evidence for the occurrence of multiple adenosine receptor-mediated modulation of noradrenaline release in the rat tail: inhibition mediated by adenosine A(1) receptors and facilitation mediated by both adenosine A(2A) and A(2B) receptors. (C) 2004 Elsevier B.V. All rights reserved.