Functional characterization of three adenosine receptor types.
1. The purpose of the present study was to classify adenosine receptors into A1 and A2 subtypes in a wide range of isolated tissues and cell types (rat adipocytes and atria, guinea-pig ileum and atria (A1); guinea-pig aorta, dog coronary artery and human platelets and neutrophils (A2)) using the R- and S-diastereoisomers of N-phenylisopropyladenosine (PIA), N-cyclopentyladenosine (CPA), the novel compound, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR79236), N-[(2-methylphenyl)methyl]adenosine (metrifudil), 2-(phenylamino)adenosine (CV1808), and 2[[2-[4-(2-carboxyethyl)phenyl]ethyl]amino]-N- ethylcarboxamidoadenosine (CGS21680); N-ethylcarboxamidoadenosine (NECA) was used as a standard. 2. Results obtained in all tissue preparations previously reported to contain A1-receptors could be described by a single rank order of agonist potency: CPA > or = GR79236, R-PIA > or = NECA >> S-PAI > or = metrifudil > or = CV1808, CGS21680. 3. In contrast, two distinct rank orders of agonist potency were observed in preparations previously reported to contain A2-receptors. In dog coronary artery, human neutrophils and platelets the rank order of potency was: CV1808, CGS21680 > or = NECA > R-PIA > or = metrifudil > or = CPA > GR79236 S-PIA. However, in guinea-pig aorta the rank order was: NECA > metrifudil > R-PIA, CPA > CV1808, GR79236 > or = S-PIA, CGS21680. 4. The results of this study are consistent with the existence of three types of adenosine receptor: A1-and two subtypes of A2-receptor. The receptor present in dog coronary artery, human platelets and neutrophils, probably corresponds to the A2a subtype, whilst that present in the guinea-pig aorta may be of the A2b subtype.
Gurden
M F
MF
Pharmacology Division, Glaxo Group Research, Ware, Hertfordshire.
Coates
J
J
Ellis
F
F
Evans
B
B
Foster
M
M
Hornby
E
E
Kennedy
I
I
Martin
D P
DP
Strong
P
P
Vardey
C J
CJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D010627:Phenethylamines; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C027512:1,3-diethyl-8-phenylxanthine; D019830:Adenosine-5'-(N-ethylcarboxamide); C082872:metrifudil; D013806:Theophylline; C028322:8-phenyltheophylline; C026708:2-phenylaminoadenosine; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine; D009638:Norepinephrine