Slowing of shortening velocity of rat cardiac myocytes by adenosine receptor stimulation regardless of beta-adrenergic stimulation.
1. Single ventricular myocytes were enzymatically isolated, incubated with the A1-purinergic and beta-adrenergic receptor-specific agonists N6-cyclopentyladenosine (CPA) and isoprenaline (Iso), and then rapidly skinned. Ca2+ sensitivity of isometric tension and unloaded shortening velocity (Vo) were measured, and protein kinase A (PKA)-specific phosphorylations of troponin I (TnI) and C-protein were assessed by back-phosphorylation of cell suspensions with [gamma-32P]-ATP. 2. Isoprenaline treatment decreased the Ca2+ sensitivity of isometric tension relative to propranolol-treated controls, as did simultaneous stimulation with Iso and CPA (Iso + CPA). CPA alone had no effect on Ca2+ sensitivity. Vo was greater in Iso-treated cells than in paired controls, while Vo was significantly less than control in both Iso + CPA-treated and CPA-treated cells. 3. Phosphorylation of TnI and C-protein was increased by Iso treatment and also when Iso and CPA were simultaneously applied. CPA alone caused a significant decrease in the phosphorylation state of these two proteins. 4. From these results we conclude that A1-purinergic receptor stimulation does not inhibit beta-adrenergic receptor-mediated phosphorylation of myofilament proteins, nor does it alter the Ca2+ sensitivity of isometric tension at the level of the myofilaments. However, A1-receptor stimulation does decrease Vo at the level of the myofilaments by a mechanism that is independent of beta-adrenergically mediated phosphorylation of TnI and C-protein.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007537:Isometric Contraction / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D010766:Phosphorylation; D011433:Propranolol / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D009124:Muscle Proteins; D058906:Purinergic P1 Receptor Agonists; C048599:N(6)-cyclopentyladenosine; D011433:Propranolol; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium