Selective A2-Adenosine Receptor Agonists Do Not Alter Action Potential Duration, Twitch Shortening, or cAMP Accumulation in Guinea Pig, Rat, or Rabbit Isolated Ventricular Myocytes

• Published in: Circulation research 1993-01, Vol.72 (1), p.194-205
• Main Authors: Shryock, John, Song, Yejia, Wang, Desuo, Baker, Stephen P, Olsson, Ray A, Belardinelli, Luiz
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosine-5'-(N-ethylcarboxamide); Animals; Biological and medical sciences; Cell Line - drug effects; Colforsin - pharmacology; Cyclic AMP - metabolism; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Heart; Heart - drug effects; Myocardium - metabolism; Rabbits; Rats; Receptors, Purinergic - analysis; Vertebrates: cardiovascular system
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.72.1.194

In this study, the hypothesis that mammalian ventricular myocytes possess A2-adenosine receptors was tested. Electrophysiological, contractile, and cAMP responses to the selective A2-adenosine receptor agonists 2-[2-(4-methylphenyl)ethoxyladenosine (WRC-0090) and 2-(2-cyclohexylethoxy)adenosine (WRC-0013) and the nonselective adenosine receptor agonist 5ʼ-(N-ethylcarboxamido)adenosine (NECA) were measured using ventricular myocytes isolated from guinea pig, rabbit, and rat hearts. Pertussis toxin pretreatment and/or the selective A,-adenosine receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and (±) N-endonorbornan-2-yl-9-methyladenine (N-0861) were used to prevent activation of A1-adenosine receptors on these cells. Action potential duration at 50% repolarization was not altered by WRC-0090, NECA, or WRC-0013 with or without 0.1 μM DPCPX or pertussis toxin pretreatment, and WRC-0090 and NECA failed to prolong the action potential duration of myocytes exposed to 0.1 or 1 μM forskolin. WRC-0090 alone or with 0.1 μM DPCPX did not increase the amplitude of shortening of pertussis toxin-treated or untreated myocytes, and WRC-0090 or NECA did not significantly increase cAMP accumulation. In contrast to these results with myocytes, in the smooth muscle cell line DIT1MF-2 the effect of both selective A2-agonists on cAMP accumulation was biphasiclow concentrations (≤0.3 μM) increased but higher concentrations decreased accumulation of cAMP. The decreased cAMP accumulation seen at higher agonist concentrations was completely abolished by either 0.1 μM DPCPX or pretreatment of cells with pertussis toxin. In summary, the results of the present study do not provide evidence for A2-adenosine receptors on mammalian ventricular cardiomyocytes but confirm reports of the coexistence of both A1 and A2 subtypes of adenosine receptors on 1DT1MF-2 cells.