5. (30 pts) Adenosine receptors (ARS) belong to the family of G protein-coupled rectptors. There are four subtypes of ARS (A1, A2A, A2B, and A3) that all respond to the nucleoside adenosine. The AIR four subtypes of ARs (A1, A2A, AR. and A. and A2AR regulate myocardial oxygen consumption and coronary blood flow. the A2B and A3 receptors are located mainly peripherally and are involved in processes such as inflammation an immune responses. The AIR couple to the Gai family of G proteins and inhibit production of Mr White A2R couples to the Gas subunit, stimulating adenylyl cyclase to elevate cAMP levels. 5'-N-Ethylcarboxamidoadenosine (NECA) is a well-studied agonist of AR's. Dose-response curves were determined for NECA, adenosine, 2-chloro-N6-cyclopentyladenosine (CCPA) and CGS-21680. EN NH HO NH2 NH2 HO OH NVN HO OH NN HO OH Adenosine NECA ССРРEN NH2 HO OH NYN NHS CSG-21680 co2H A A,R - GPA1/Gayu. AzAR-GPA1/Ga, AR-GPA1/Gr. 100- TOD Percentage NECA maximum Percentage NECA maximum Percentage NECA maximum Log (Ligand] M 5 AR-GPA1/Gaju Log (Ligand] M 1 A,R-GPA1#Gayn Log (Ligand] M 5 AzAR-GPA1/Ga, Selectivity Factor ? ? ? Selectivity Factor Selectivity Factor AZAR-GPA1/G, AzaR-GPA1/Goa, AzR-GPA1/Go, Adenosine CCPA cas21680 Adenonino ccPA cas21680 Adenosine ccPA CGs21680 Figure 1. AR agonists display receptor subtype selectivity. Dose-response curves for various AR agonists (A) AIR, (B) AZAR, and (C) A2BR following stimulation with (O) NECA, (O) adenosine, (O) CCPA, or (0) CGS-21680. Activation of the reporter gene was calculated and is expressed as the percentage of the maximum response achieved when cells were stimulated with the reference agonist NECA.