2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor.
A Langendorff guinea pig heart preparation served for the assay of agonist activity of a series of 24 2-alkoxyadenosines at the A1 and A2 adenosine receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). Activities are low at the A1 receptor and do not show a clear relationship to the size or hydrophobicity of the C-2 substituent. All the analogues are more potent at the A2 receptor, activity varying directly with the size and hydrophobicity of the alkyl group. The most potent analogue in this series, 2-(2-cyclohexylethoxy)adenosine has an EC50 of 1 nM for coronary vasodilation and is 8700-fold selective for the A2 receptor.
Ueeda
M
M
Department of Internal Medicine, University of South Florida, Tampa 33612.
Thompson
R D
RD
Arroyo
L H
LH
Olsson
R A
RA
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D051381:Rats; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship
D011983:Receptors, Purinergic; D000241:Adenosine