FUNCTIONAL-CHARACTERIZATION OF 3 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); guin ea-pig aorta, dog coronary artery and human platelets and neutrophils (A2)) using the R- and S-diastereoisomers of N-phenylisopropyladenosin e (PIA), N-cyclopentyladenosine (CPA), the novel compound, N-[(1S,tran s)-2-hydroxycyclopentyl]adenosine (GR79236), N-[(2-methylphenyl)methyl ]adenosine (metrifudil), 2-(phenylamino)adenosine (CV1808), and yl)phe nyl]ethyl)amino]-N-ethylcarboxamidoadenosine (CGS21680); N-ethylcarbox amidoadenosine (NECA) was used as a standard. 2 Results obtained in al l tissue preparations previously reported to contain A1-receptors coul d be described by a single rank order of agonist potency: CPA greater- than-or-equal-to GR79236, R-PIA greater-than-or-equal-to NECA > > S-PI A greater-than-or-equal-to metrifudil greater-than-or-equal-to CV 1 80 8, CGS21680. 3 In contrast, two distinct rank orders of agonist potenc y were observed in preparations previously reported to contain A2-rece ptors. In dog coronary artery, human neutrophils and platelets the ran k order of potency was: CV1808, CGS21680 greater-than-or-equal-to NECA > R-PIA greater-than-or-equal-to metrifudil greater-than-or-equal-to CPA > GR79236, S-PIA. However, in guinea-pig aorta the rank order was: NECA > metrifudil > R-PIA, CPA > CV1808, GR79236 greater-than-or-equa l-to S-PIA, CGS21680. 4 The results of this study are consistent with the existence of three types of adenosine receptor: A1-and two subtype s of A2-receptor. The receptor present in dog coronary artery, human p latelets and neutrophils, probably corresponds to the A2a subtype, whi lst that present in the guinea-pig aorta may be of the A2b subtype.