title: Functional and RNA expression profile of adenosine receptor subtypes in mouse mesenteric arteries.
abstract: Concentration-response curves (CRCs) of adenosine receptor (AR) agonists, NECA (nonspecific), CCPA (A1 specific), CGS-216870 (A2A specific), BAY 60-6583 (A2B specific), and Cl-IB-MECA (A3 specific) for mesenteric arteries (MAs) from 4 AR knockout (KO) mice (A1, A2A, A2B, and A3) and their wild type (WT) were constructed. The messenger RNA expression of MAs from KO mice and WT were also studied. Adenosine (10 to 10 M) and NECA (10 to 10 M) induced relaxation in all mice except A2B KO mice, which only showed constriction by adenosine at 10 to 10 and NECA at 10 to 10 M. The CCPA induced a significant constriction at 10 and 10 M in all mice, except A1KO. BAY 60-6583 induced relaxation (10 to 10 M) in WT and no response in A2BKO except at 10 M. The CRCs for BAY 60-6583 in A1, A2A, and A3 KO mice shifted to the left when compared with WT mice, suggesting an upregulation of A2B AR. No responses were noted to CGS-21680 in all mice. Cl-IB-MECA only induced relaxation at concentration greater than 10 M, and no differences were found between different KO mice. The CRC for Bay 60-6583 was not significantly changed in the presence of 10 M of L-NAME, 10 M of indomethacin, or both. Our data suggest that A2B AR is the predominant AR subtype and the effect may be endothelial independent, whereas A1 AR plays a significant modulatory role in mouse MAs.
authors.affiliation: Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV 26506, USA. bteng@hsc.wvu.edu
authors.forename: Bunyen
authors.initials: B
authors.lastname: Teng
authors.forename: Daniel
authors.initials: D
authors.lastname: Fil
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Tilley
authors.forename: Catherine
authors.initials: C
authors.lastname: Ledent
authors.forename: Thomas
authors.initials: T
authors.lastname: Krahn
authors.forename: S Jamal
authors.initials: SJ
authors.lastname: Mustafa
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D043684:Receptor, Adenosine A3 / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058906:Purinergic P1 Receptor Agonists; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1