Adenosine A2a-receptor activation enhances cardiomyocyte shortening via Ca2+-independent and -dependent mechanisms.
Adenosine A2a receptor (A2aR) stimulation enhances the shortening of ventricular myocytes. Whether the A2aR-mediated increase in myocyte contractility is associated with alterations in the amplitude of intracellular Ca2+ transients was investigated in isolated, contracting rat ventricular myocytes using the Ca2+-sensitive fluorescent dye fura 2-AM. In the presence of intact inhibitory G protein pathways, 10(-4) M 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680), an A2aR agonist, insignificantly increased Ca2+ transients by 8 +/- 5%, whereas myocyte shortening increased by 54 +/- 1%. In contrast, 2 x 10(-7) M isoproterenol, a beta-adrenergic receptor agonist, increased Ca2+ transients by 104 +/- 15% and increased myocyte shortening by 61 +/- 6%. When A2aR were stimulated in myocytes that had the antiadrenergic actions of adenosine (Ado) abolished by either treatment with pertussis toxin (PTx) or the presence of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an adenosine A1-receptor antagonist, the maximum increases in Ca2+ transients were similarly nominal (with PTx: 10(-4) M CGS-21680, 14 +/- 6% and 10(-4) M Ado, 15 +/- 4%; without PTx: 10(-5) M Ado + 2 x 10(-7) M DPCPX, 19 +/- 1%). These results indicate that compared with beta-adrenergic stimulation, which markedly increases myocyte Ca2+ transients and shortening, A2aR-mediated increases in myocyte shortening are accompanied by only modest increases in Ca2+ transients. These observations suggest that the A2aR-induced contractile effects are mediated predominantly by Ca2+-independent inotropic mechanisms.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002338:Carotenoids / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000166:cytology*; D010105:Oxygenases / Q000494:pharmacology; D037342:Pertussis Toxin; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology