Antagonist pharmacology of adenosine A2B receptors from rat, guinea pig and dog.
We have sought evidence for species differences between adenosine A2B receptors by comparing the potencies of eight adenosine receptor antagonists, representing four different chemical classes, at the native adenosine A2B receptors which mediate relaxation of smooth muscle from rat colon, guinea pig aorta and dog saphenous vein. In all three assays, the antagonists caused parallel rightward shifts in the concentration-response curves to NECA and there was no depression of the maximum responses. There were highly significant correlations between the pKB values on each of the three receptors. However, the pKB values of 8-SPT (8-p-(sulphophenyl)theophylline), XAC (8-[-[[[[(2-aminoethyl)amino]-carbonyl]methyl]oxy]phenyl]-1,3-dipropylxanthine), CGS 15943 (9-chloro-2,2-(furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine) and CGH 2473 N-[4-(3,4-dichloro-phenyl)-5-pyridin-4-yl-thiazol-2-yl]-acetamide) for the dog receptor exceeded by at least 0.5 log units the pKB values at the rat and guinea pig sites. Our data indicate species differences between the rat and guinea pig adenosine A2B receptors on the one hand and the dog adenosine A2B receptor on the other with respect to antagonist pharmacology.
Fozard
John R
JR
Research Department, Novartis Pharma AG, WSJ-386.510, CH-4002 Basel, Switzerland. john_r.fozard@pharma.novartis.com
Baur
Francois
F
Wolber
Cedric
C
D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D013045:Species Specificity; D014230:Triazoles / Q000494:pharmacology
D058917:Adenosine A2 Receptor Antagonists; D011799:Quinazolines; D043704:Receptor, Adenosine A2B; D014230:Triazoles; D019830:Adenosine-5'-(N-ethylcarboxamide); C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine