Functional and RNA Expression Profile of Adenosine Receptor Subtypes in Mouse Mesenteric Arteries

Concentration-response curves (CRCs) of adenosine receptor (AR) agonists, NECA (nonspecific), CCPA (A(1) specific), CGS-216870 (A(2A) specific), BAY 60-6583 (A(2B) specific), and Cl-IB-MECA (A(3) specific) for mesenteric arteries (MAs) from 4 AR knockout (KO) mice (A(1), A(2A), A(2B), and A(3)) and their wild type (WT) were constructed. The messenger RNA expression of MAs from KO mice and WT were also studied. Adenosine (10(-5) to 10(-4) M) and NECA (10(-6) to 10(-5) M) induced relaxation in all mice except A(2B) KO mice, which only showed constriction by adenosine at 10(-6) to 10(-4) and NECA at 10(-8) to 10(-5) M. The CCPA induced a significant constriction at 10(-8) and 10(-7) M in all mice, except A(1)KO. BAY 60-6583 induced relaxation (10(-7) to 10(-5) M) in WT and no response in A(2B)KO except at 10(-5) M. The CRCs for BAY 60-6583 in A(1), A(2A), and A(3) KO mice shifted to the left when compared with WT mice, suggesting an upregulation of A(2B) AR. No responses were noted to CGS-21680 in all mice. Cl-IB-MECA only induced relaxation at concentration greater than 10(-7) 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(-5) M of L-NAME, 10(-6) M of indomethacin, or both. Our data suggest that A(2B) AR is the predominant AR subtype and the effect may be endothelial independent, whereas A(1) AR plays a significant modulatory role in mouse MAs.