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.
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. PACPX antagonized the actions of adenosine in both types of preparation and was a more potent antagonist than 8-phenyltheophylline. The antagonism at the A2-purinoceptor was competitive with a pA2 of 5.95. 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. 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.
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D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D004176:Dipyridamole / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011983:Receptors, Purinergic; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D014970:Xanthines; D004176:Dipyridamole; D013806:Theophylline; C028322:8-phenyltheophylline; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine; D009638:Norepinephrine