Pharmacological Evidence for A1 and A2 Adenosine Receptors in the Skin Microcirculation

• Published in: Circulation research 1989-07, Vol.65 (1), p.176-184
• Main Authors: Stojanov, Igor, Proctor, Kenneth G
• Format: Article
• Language: English
• Subjects: Animals; Arterioles - drug effects; Arterioles - physiology; Biological and medical sciences; Cricetinae; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Male; Mesocricetus; Microcirculation; Osmolar Concentration; Receptors, Purinergic - drug effects; Receptors, Purinergic - metabolism; Receptors, Purinergic - physiology; Skin - blood supply; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Vertebrates: skin, associated glands, phaneres, light organs, various exocrine glands (salt gland, uropygial gland...), adipose tissue, connective tissue
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.65.1.176

To characterize adenosine-mediated vascular responses, synthetic A1 and A2 receptor agonists (N-ethyl carboxamido adenosine [NECA], 2-chloro adenosine [2CA], or cyclohexyl adenosine [CHA]), the parent compound (adenosine [ADO]), an uptake inhibitor (dipyridamole [DIPYRID]) or a nonselective, competitive antagonist (8-phenyl theophylline [8pTHEO]) were topically applied to 20–60 μm arterioles in the subcutaneous microcirculation of the hamster. Blood flow was calculated from arteriolar diameter and red blood cell velocity using intravital microscopy. At >10 M, the potency order for vasodilation (maximum, 170–190% of control) was NECA>2CA>ADO; these responses were attenuated by 10 M 8pTHEO. From 10 to 10 M, 2CA evoked vasodilation whereas ADO, which has an identical affinity at A1 and A2 receptors, evoked lesser responses. ADO-induced vasodilation was potentiated by 10 M DIPYRID; this response was similar to that evoked by 2CA alone or 2CA+DIPYRID. In contrast to ADO, 2CA is a poor substrate for cellular uptake, which suggests that uptake reduces the A2 effect of exogenous ADO. From 10 to 10 M, CHA and ADO were equipotent for causing vasoconstriction (minimum, 80–90% of control); these responses were completely antagonized by SpTHEO. Norepinephrine was a more potent vasoconstrictor and 8pTHEO did not alter these responses. Since ADO is a metabolic substrate and a nonselective receptor agonist, while CHA is Arselective and a poor substrate for cellular uptake, neither A2 activation nor cellular uptake altered expression of the A1 effect of exogenous ADO. Furthermore, DIPYRID had no effect on the A1 response. Thus, depending on agonist concentration, stimulation of high affinity A1 receptors or low affinity A2 receptors can cause opposite responses in the skin microcirculation. The precise location or physiological role of these receptors is unknown.