Selective attenuation of isoproterenol-stimulated arrhythmic activity by a partial agonist of adenosine A1 receptor.
BACKGROUND
The goal of this study was to examine the hypothesis that a partial agonist of the adenosine A1 receptor (A1AdoR) may cause a greater attenuation of catecholamine-induced ventricular arrhythmic activity than of contractility.


RESULTS
The effects of CVT-2759 and adenosine, a partial and a full agonist of the A1AdoR, on isoproterenol-stimulated arrhythmic activity and contractility of guinea pig isolated ventricular myocytes were determined. CVT-2759 (10 micromol/L) and adenosine (10 micromol/L) significantly inhibited isoproterenol-induced arrhythmic activity (aftercontraction and transient inward current) but did not reduce the amplitudes of twitch shortening and L-type Ca2+ current. Increasing the concentration of the full agonist adenosine from 10 to 100 micromol/L, however, caused significant attenuation of twitch shortening as well as aftercontractions, whereas increasing the concentration of the partial agonist CVT-2759 from 10 to 100 micromol/L did not. CVT-2759 also significantly inhibited isoproterenol-induced spontaneous ventricular beats in isolated hearts. In contrast to adenosine, CVT-2759 neither activated adenosine-sensitive K+ current nor shortened the duration of the atrial APD.


CONCLUSIONS
The present results support the hypothesis and suggest a potential role for a partial agonist of the A1AdoR in the treatment of cardiac arrhythmias.
Song
Yejia
Y
Department of Medicine, University of Florida, Gainesville, FL 32610, USA. songy@medicine.ufl.edu
Wu
Lin
L
Shryock
John C
JC
Belardinelli
Luiz
L
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D011687:Purines / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D058906:Purinergic P1 Receptor Agonists; D011687:Purines; C419102:CVT 2759; D000241:Adenosine; D007545:Isoproterenol