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

xanthine (PACPX) was examined for its ability to antagonize adenosine acting on the Al and A2 subclasses of the P1-purinoceptor. Al-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 Alpurinoceptor was greater than that at the A2-purinoceptor, based on a comparison of pD2 values. 5 The manner ofantagonism of PACPX on the A1-purinoceptors ofthe 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 Al subclasses of P,-purinoceptor.

KW‐3902, a selective high affinity antagonist for adenosine A1 receptors

“…The antagonism was not competitive with a slope factor of 1.40 + 0.058 from the Schild plot and it showed a mixed type inhibition at the binding assay using rat brain membranes. A similar inhibition type has been noted for PACPX (Burnstock & Hoyle, 1985), although the cause remains unclear. The apparent KB value (0.34 nM) corresponded to the binding affinity for the A1 receptor in rat brain membrane (Ki value: 0.19 nM).…”

Apparent affinity of some 8‐phenyl‐substituted xanthines at adenosine receptors in guinea‐pig aorta and atria

“…This suggestion is supported by the similar behaviour of the compound in aortic preparations. Burnstock & Hoyle (1985) have also observed that increasing the concentration of PACPX beyond 2 JAM did not evoke a greater antagonism at adenosine receptors in the guinea-pig atrium or taenia coli.…”

1,3,8‐ and 1,3,7‐substituted xanthines: relative potency as adenosine receptor antagonists at the frog neuromuscular junction

“…This indicates that the antagonist proffle of the adenosine receptor at the frog neuromuscular junction is different from the antagonist profile of the A1-adenosine receptor. Even excluding PACPX, which in some preparations behaves as a noncompetitive antagonist of adenosine receptors (Burnstock & Hoyle, 1985;Collis et al, 1987;Wil- The ability of 1,3,8-substituted xanthine derivatives to inhibit NECA-induced stimulation of adenylate cyclase in human platelets has been studied in order to characterize the antagonist proffle of the A2-adenosine receptor Ukena et al, 1986b;Lohse et al, 1987). In these studies it was shown that XAC (Ki = 24-25nM) > DPX (210nM), DPCPX (390nM), PACPX (470 nM) > 8-PT (1.9-4.1 pM), XCC (2.4 gM).…”