Correlation of adenosine receptor affinities and cardiovascular activity.
Binding affinities of 28 adenosine analogs at A1 adenosine receptors (rat whole brain membranes, [3H]N6-cyclohexyladenosine, CHA), and at A2 adenosine receptors (rat striatal membranes, [3H]NECA) were compared to their EC25 values for decreasing heart rate and increasing coronary flow in the isolated rat heart. Heart rate (an A1 response) correlated with A1 binding affinity (r2 = 0.71, p less than 0.0001) but not with A2 binding affinity (r2 = 0.007, n.s.); conversely, coronary flow (an A2 response) correlated with A2 binding affinity (r2 = 0.83, p less than 0.0001) but not with A1 binding affinity (r2 = 0.05, n.s.). These results confirm that the brain A1 and A2 receptors, studied by binding methods, bear close similarities to their respective counterparts in the heart, studied by means of functional responses.
Hamilton
H W
HW
Department of Chemistry, Warner-Lambert/Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105.
Taylor
M D
MD
Steffen
R P
RP
Haleen
S J
SJ
Bruns
R F
RF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism / Q000502:physiology*
D011983:Receptors, Purinergic; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine