Functional characterization of three adenosine receptor types

Abstract

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. Results obtained in all tissue preparations previously reported to contain A1‐receptors could be described by a single rank order of agonist potency: CPA ≥ GR79236, R‐PIA ≥ NEC A > > S‐PIA ≥ metrifudil ≥ CV1808, CGS21680. 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 ≥ NECA > R‐PIA ≥ metrifudil ≥ CPA > GR79236, S‐PIA. However, in guinea‐pig aorta the rank order was: NECA > metrifudil > R‐PIA, CPA > CV1808, GR79236 ≥ S‐PIA, CGS21680. 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. 1993 British Pharmacological Society