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 A1 receptor-selective agonist N6-cyclopentyladenosine (CPA; 1-100 nM) and the non-selective adenosine receptor agonist N-ethylcarboxamidoadenosine (NECA; 1-10 microM) decreased tritium overflow. These effects were blocked by the adenosine A1 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-ethylcarboxamido adenosine (CGS 21680; 1-100 nM) enhanced tritium overflow, an effect blocked by the adenosine A(2A) 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-selective antagonist N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-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. Immunohistochemistry revealed immunoreactivity for all adenosine-receptor subtypes. Areas of co-localization were found for neurofilament with adenosine A1, A(2A) and A(2B) but not A3 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 A1 receptors and facilitation mediated by both adenosine A(2A) and A(2B) receptors.
Diniz
Carmen
C
Serviço de Farmacologia, CEQOFFUP, Faculdade de Farmácia, Universidade do Porto, Rua Anibal Cunha, 164, P 4050-047 Porto, Portugal.
Fresco
Paula
P
Leal
Sandra
S
Gonçalves
Jorge
J
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001158:Arteries; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013623:Tail / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014230:Triazoles; D019830:Adenosine-5'-(N-ethylcarboxamide); D009638:Norepinephrine