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Functional characterization of three adenosine receptor types
Author(s) -
Gurden M.F.,
Coates J.,
Ellis F.,
Evans B.,
Foster M.,
Hornby E.,
Kennedy I.,
Martin D.P.,
Strong P.,
Vardey C.J.,
Wheeldon A.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13629.x
Subject(s) - adenosine , adenosine receptor , agonist , receptor , medicine , endocrinology , guinea pig , aorta , biology , potency , pharmacology , chemistry , biochemistry , in vitro
1 The purpose of the present study was to classify adenosine receptors into A 1 and A 2 subtypes in a wide range of isolated tissues and cell types (rat adipocytes and atria, guinea‐pig ileum and atria (A 1 ); guinea‐pig aorta, dog coronary artery and human platelets and neutrophils (A 2 )) 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 A 1 ‐receptors could be described by a single rank order of agonist potency: CPA ≥ GR79236, R ‐PIA ≥ NEC A > > S‐PIA ≥ metrifudil ≥ CV1808, CGS21680. 3 In contrast, two distinct rank orders of agonist potency were observed in preparations previously reported to contain A 2 ‐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. 4 The results of this study are consistent with the existence of three types of adenosine receptor: A 1 ‐and two subtypes of A 2 ‐receptor. The receptor present in dog coronary artery, human platelets and neutrophils, probably corresponds to the A 2a subtype, whilst that present in the guinea‐pig aorta may be of the A 2b subtype.