Regulation of adenosine receptor system in coronary artery: functional studies and cAMP

Regulation of the adenosine receptor system was investigated using a new in vitro model of porcine coronary artery after exposure to an adenosine receptor agonist. Isolated coronary arteries were incubated in the absence (control) and presence (treated) of 2-chloroadenosine (CAD) in culture media (pH 7.4) at 37 degrees C with 92.5% O2-7.5% CO2. CAD treatment led to a significant rightward shift in the relaxation responses to the adenosine receptor agonists CAD, 5'-(N-ethylcarboxamido)adenosine, and R-phenylisopropyladenosine. The shift was both concentration and time dependent and was maximum at 100 microM at 3 days. The relaxation responses to isoproterenol and sodium nitroprusside were unaltered under identical conditions. Forskolin-mediated relaxation was also shifted rightward in the treated group. The shift in CAD- and forskolin-mediated relaxation in the treated group was endothelium independent. On the other hand, isoproterenol (10 microM, 3 days) treatment produced a rightward shift in the relaxation response to isoproterenol, while the response to CAD was unaltered. In a separate set of experiments, CAD did not stimulate adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in the treated arteries compared with control. However, NaF and forskolin stimulation of cAMP was markedly decreased in the treated group. Unlike these agonists, isoproterenol stimulation of cAMP was similar in both treated and control groups. The data suggest the desensitization of the adenosine receptor via regulation of stimulatory guanine nucleotide binding proteins without altering the beta-receptor-mediated responses in coronary artery.