CARDIAC ADENOSINE RECEPTORS

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This project tests a number of predictions of the hypothesis that adenosine is a physiological regulator of coronary flow and cardiac performance. These include the predictions that the purine dipole moment and the stereoselective interaction of exocyclic purine substituents with specialized regions of the coronary adenosine receptor determine the vasoactivity of adenosines and antagonism by theophyllines. These studies employ C2 and C6 substituted nebularines and N1 and N3 alkylxanthines. Tests of the hypothesis that the anti-N-g+ conformer of adenosine binds to the receptor employs 2 feet-substituted 2 feet-deoxyadenosines. Studies testing the hypothesis that there are regional differences in the type of adenosine R receptors employ enzymatically dispersed cardiocytes and adenosine analogs covalently linked to dextrans to prevent penetration into cells.