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

Open Access
Publisher Website
Google Scholar
Abstract
1 Some 8-phenyl-substituted, 1,3 dipropyl xanthines have previously been demonstrated to have a 20–400 fold greater affinity for A1 binding sites in rat CNS membranes than for A2 adenosine receptors in intact CNS cells from guinea-pigs. In the present study these compounds (1,3, dipropyl-8-phenylxanthine: DPPX; 1,3 dipropyl-8-(2 amino-4-chlorophenyl) xanthine: PACPX; 8-(4-(2-aminoethyl)amino) carbonyl methyl oxyphenyl)-1,3-dipropylxanthine: XAC; and d-Lys-XAC) together with two that have not been reported to exhibit A1-receptor selectivity (8-(p-sulphophenyl)theophylline: 8-PST; 8-(4-carboxy methyl oxyphenyl)-1,3-dipropylxanthine: XCC) have been evaluated as antagonists of the effects of 2-chloroadenosine in two isolated cardiovascular tissues. 2 The isolated tissues used were guinea-pig atria (bradycardic response) and aorta (relaxation), which are thought to possess A1 and A2 adenosine receptors, respectively. 3 All the xanthines antagonized responses evoked by 2-chloroadenosine in both tissues but did not affect responses evoked by acetylcholine (atria) or sodium nitrite (aorta). 4 The xanthines, 8-PST, XAC, d-Lys XAC, XCC and DPPX appeared to be competitive antagonists of the effects of 2-chloroadenosine, as Schild plot slopes did not differ significantly from unity. The 1,3-dipropyl substituted compounds had pA2 values from 6.5 to 7.4 and were more potent than the 1,3 dimethyl substituted 8-PST (pA2 4.9 to 5). 5 For individual xanthines, there was no difference between pA2 values obtained in the atria and in the aorta. 6 Responses evoked by 2-chloroadenosine in atria and aorta were antagonized to a similar degree by PACPX (1 μm). The agonist dose-ratio evoked by 10 μm PACPX was no greater than that evoked by 1 μm of the xanthine in both tissues. This was probably a consequence of the limited aqueous solubility of PACPX. 7 These results fail to demonstrate A1 receptor selectivity for DPPX, XAC, d-Lys XAC or PACPX in tissues from the guinea-pig. The A1 selectivity previously found for these compounds may therefore be due to their high affinity for binding sites in rat CNS cell membranes.

This publication has 17 references indexed in Scilit: