Evidence of direct activation of adenosine A1 receptor by 5'-adenosine monophosphate in isolated guinea pig atrial myocytes.
The electrophysiological effect of 5'-adenosine monophosphate (AMP) was examined in isolated atrial myocytes of guinea pig. Membrane potential and ionic currents were measured by the tight-seal, whole-cell patch-clamp technique. AMP caused the shortening of atrial action potential in a dose-dependent manner. In voltage-clamp experiments, AMP (3-10 microM) caused the activation of IKACh as well as the decrease in basal ICa. Prolongation of action potential duration caused by isoproterenol (20 nM) was antagonized by AMP (10 microM). Isoproterenol (20 nM) occasionally caused the sustained rhythmic activity and the subsequent application of AMP (10 microM) terminated it. AOPCP (10 microM), which inhibits 5'-nucleotidase and hence prevents breakdown of AMP, did not significantly attenuate the effect of AMP on shortening action potential. However, the application of adenosine deaminase (1 U/ml), which deaminates adenosine to inosine, partially reversed the shortening of action potential caused by AMP (10 microM). These results indicate that (1) AMP could activate IKACh and decrease basal ICa simultaneously, and antagonize the isoproterenol-stimulated action potential prolongation; and (2) the observed electrophysiological effect of AMP in whole-cell preparation is attributed to AMP per se as well as its degradative product, adenosine.
Wu
S N
SN
Graduate Institute of Medicine, Kaohsiung Medical College, Taiwan, R.O.C.
Lin
Y T
YT
Chen
S S
SS
D000200:Action Potentials / Q000187:drug effects; D000243:Adenosine Deaminase / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism
D011983:Receptors, Purinergic; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000243:Adenosine Deaminase; D007545:Isoproterenol