Antagonism of adenosine-induced relaxation by methylxanthines in coronary artery

Adenosine plays an important role in the regulation of coronary blood flow, as it relaxes the coronary smooth muscle through A2 receptors. Methylxanthines have been used to antagonize the A1 and A2 adenosine receptors in various tissues. The aim of the present study was to investigate the antagonistic profile of methylxanthines towards A2 adenosine receptor in bovine coronary arteries. 8-p-sulpho-phenyltheophylline (8-SPT), 1,3-diethyl-8-phenyl xanthine (DPX) and 8-phenyltheophylline (8-PT) shifted the concentration-response curve for NECA to the right in parallel. Enprofylline (EN) did not shift significantly the concentration-response for NECA to the right. 1,3-Dipropyl-8-(2-amino-4-chloro) phenylxanthine (PACPX) shifted the concentration-response curve for NECA to the right and showed a probable noncompetitive antagonism. Based on the KB values, the relative order of potency for the methylxanthine analogs were 8-SPT greater than DPX greater than PACPX greater than 8-PT greater than EN. The data suggest that 8-ST and DPX are potent A2 adenosine receptor antagonists.