title: Adenosine A2A receptor modulation of juvenile female rat skeletal muscle microvessel permeability.
abstract: Little is known of the regulation of skeletal muscle microvascular exchange under resting or stimulating conditions. Adenosine (ADO) levels in skeletal muscle increase during physiological (exercise) and pathological (hypoxia, inflammation, and ischemia) conditions. Later stages of these pathologies are characterized by the loss of vascular barrier integrity. This study focused on determining which ADO receptor mediates the robust reduction in microvessel permeability to rat serum albumin (P(s)(RSA)) observed in juvenile female rats. In microvessels isolated from abdominal skeletal muscle, ADO suffusion induced a concentration-dependent reduction in arteriolar [log(IC(50)) = -9.8 +/- 0.2 M] and venular [log(IC(50)) = -8.4 +/- 0.2 M] P(s)(RSA). RT-PCR and immunoblot analysis demonstrated mRNA and protein expression of ADO A(1), A(2A), A(2B), and A(3) receptors in both vessel types, and immunofluorescence assay revealed expression of the four subtype receptors in the microvascular walls (endothelium and smooth muscle). P(s)(RSA) responses of arterioles and venules to ADO were blocked by 8-(p-sulphophenyl)theophylline, a nonselective A(1) and A(2) antagonist. An A(2A) agonist, CGS21680, was more potent than the A(1) agonist, cyclopentyladenosine, or the most-selective A(2B) agonist, 5'-(N-ethylcarboxamido)adenosine. The ability of CGS21680 or ADO to reduce P(s)(RSA) was abolished by the A(2A) antagonist, ZM241385. An adenylyl cyclase inhibitor, SQ22536, blocked the permeability response to ADO. In aggregate, these results demonstrate that, in juvenile females (before the production of the reproductive hormones), ADO enhances skeletal muscle arteriole and venule barrier function predominantly via A(2A) receptors using activation of adenylyl cyclase-signaling mechanisms.
authors.affiliation: Dept. of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA.
authors.forename: Jianjie
authors.initials: J
authors.lastname: Wang
authors.forename: Virginia H
authors.initials: VH
authors.lastname: Huxley
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000502:physiology*; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000502:physiology; D012709:Serum Albumin / Q000493:pharmacokinetics; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014699:Venules / Q000166:cytology / Q000502:physiology*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D010627:Phenethylamines; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D012709:Serum Albumin; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C017759:9-(tetrahydro-2-furyl)-adenine; D000262:Adenylyl Cyclases; D000225:Adenine; D000241:Adenosine