Pharmacological analysis of vasodilation induced by extracellular adenosine 3',5'-cyclic monophosphate in the isolated and perfused canine coronary artery.

We studied how extracellular cyclic AMP (cAMP) dilates the isolated and perfused canine coronary artery using pharmacological tools. Single injections of cAMP (1-1000 nmol), adenosine 3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) (10-1000 nmol, an agonist of the cell surface cAMP receptor in Dictyostelium discoideum and of cAMP-dependent protein kinase), adenosine (0.1-1000 nmol) and 5'-AMP (0.1-1000 nmol) dilated the canine coronary artery dose dependently. The potency order for vasodilation was adenosine > 5'-AMP > cAMP > Sp-cAMPS > 8-bromo-cyclic GMP > 3'-AMP > 8-bromo-cAMP > N6,O2'-dibutyryl-cAMP. 2'-Deoxy-cAMP, 2',3'-cAMP, guanosine, cGMP, 3'-GMP and 5'-GMP did not produce vasodilation. Adenosine antagonists such as aminophylline (1-100 microM, nonselective), 8-phenyltheophylline (0.1-10 microM, A1 selective), 8-cyclopentyl-1,3-dipropylxanthine (0.01-1 microM, A1 selective) and 3,7-dimethyl-1-proparglyxanthine (0.01-1 microM, A2 selective) shifted the dose-response curve of adenosine in parallel to the right, but they shifted that of cAMP to the right and downwards. 8-Phenyltheophylline (1 and 10 microM) inhibited the response to Sp-cAMPS (100 nmol) dose dependently. Aminophylline (10 microM) did not affect isoproterenol- and forskolin-induced vasodilations. Adenosine deaminase (3 U/ml) completely inhibited the response to adenosine, but not those to 5'-AMP, cAMP, 8-bromo-cAMP and Sp-cAMPS. 5'-Nucleotidase inhibitors, adenosine-5'-(alpha,beta-methylene) diphosphate (10 microM) and 5'-GMP (1 mM), inhibited the responses to cAMP and 5'-AMP, but not that to adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)