PACPX ‐ a substituted xanthine ‐ antagonizes both the A1 and A2 subclasses of the P1‐purinoceptor: antagonism of the A2 subclass is competitive but antagonism of the A1 subclass is not

Abstract

1 1,3-Dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) was examined for its ability to antagonize adenosine acting on the A₁ and A₂ subclasses of the P₁-purinoceptor. A₁-purinoceptors were studied in the isolated, driven left atria of the guinea-pig, and A₂-purinoceptors in the isolated, carbachol-contracted taenia coli of the guinea-pig. 2 PACPX antagonized the actions of adenosine in both types of preparation and was a more potent antagonist than 8-phenyltheophylline. 3 The antagonism at the A₂-purinoceptor was competitive with a pA₂ of 5.95. 4 The antagonism at the A₁-purinoceptor was not competitive, although antagonism at the A₁-purinoceptor was greater than that at the A₂-purinoceptor, based on a comparison of pD₂ values. 5 The manner of antagonism of PACPX on the A₁-purinoceptors of the heart was different from that found for the A₁-receptors in bovine brain, implying that there is a fundamental difference between these central and peripheral A₁ subclasses of P₁-purinoceptor.