Comparison of adenosine receptor agonists with other vasodilators on noradrenaline-, potassium- and phorbol ester-contracted rabbit aorta.
Isometric contractions of rabbit isolated aortic spirals were induced by noradrenaline (1 microM), potassium chloride (51 mM) or phorbol-12,13-dibutyrate (1 microM). A cumulative concentration-response curve for adenosine, N-ethylcarboxamidoadenosine (NECA), verapamil, sodium nitroprusside, isoprenaline or forskolin was then constructed. Sodium nitroprusside displayed selectivity towards noradrenaline- compared with potassium-contracted tissues. In contrast, verapamil selectively relaxed the potassium-contracted tissues. Adenosine preferentially relaxed the noradrenaline-contracted aorta. Adenosine, in the presence of the transport inhibitor dipyridamole (10 microM), and NECA were without effect upon potassium-contracted tissues. This absolute selectivity for noradrenaline-contracted aortas indicates that adenosine A2-receptor agonists do not interfere with calcium influx through voltage-operated channels but inhibit calcium influx via receptor-operated channels or its intracellular release. The inhibition by dipyridamole of a small relaxation by adenosine in potassium-contracted tissues indicates that this was due to stimulation of an additional intracellular site. The selectivity profile of adenosine and NECA was similar to that of forskolin and isoprenaline indicating that their relaxations were due to a common activation of adenylate cyclase and cAMP accumulation. Only sodium nitroprusside- and forskolin-relaxed aortas contracted with phorbol dibutyrate. Adenosine and NECA also failed to cause relaxation of noradrenaline-contracted aortas preincubated with the phorbol ester indicating that it may desensitize A2-receptors.
Urquhart
R A
RA
Department of Pharmacology, Welsh School of Pharmacy, University of Wales College of Cardiff, U.K.
Broadley
K J
KJ
D000818:Animals; D001011:Aorta; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011983:Receptors, Purinergic / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D009638:Norepinephrine