ADENOSINE-5'-URONAMIDES RAPIDLY DESENSITIZE THE ADENOSINE-A(2) RECEPTOR IN CORONARY-ARTERY

This study examined the structure-activity-relationship (SAR) of adeno sine analogs and their ability to induce tachyphylaxis in vascular smo oth muscle. Adenosine-5'-uronamides, 5'-N-ethylcarboxamidoadenosine (N ECA), 5'-N-cyclopropylcarboxamidoadenosine (CPCA), and hyl)phenethylam ino]-5'-N-ethylcarboxamidoadenosine (CGS 21680), evidenced rapid desen sitization of the A2 vasorelaxant response in porcine coronary artery in vitro whereas adenosine, 2-chloroadenosine (CAD), or 2-[(2-cyclohex ylethyl)amino] adenosine (CGS 22492) failed to do so. Tissues with pri or exposure to NECA exhibited mitigated relaxation responses to adenos ine, CAD, and NECA but not to isoproterenol, forskolin, pinacidil, or sodium nitroprusside (SNP). The data suggest that adenosine-5'-uronami des homologously desensitize the A2 receptor in porcine coronary arter y smooth muscle.