P2 purinoceptors contribute to ATP-induced inhibition of L-type Ca2+ current in rabbit atrial myocytes.
OBJECTIVE
Adenine compounds, including adenosine-5'-triphosphate (ATP) and adenosine (Ado), exert inhibitory effects on myocardium via P1 (subtype A1) purinoceptors. However, ATP per se is a potent activator of P2 purinoceptors. Our aim was to elucidate the respective roles of P1 and P2 purinoceptors in the actions of ATP on L-type calcium current (ICa) in rabbit atrial cells.


RESULTS
A whole cell clamp technique was used to record ICa in single atrial cells from the rabbit heart. ATP (0.1 mumol/1-3 mmol/l) produced an inhibitory effect on ICa prestimulated by isoproterenol (ISO, 30 nmol/l), even in the presence of Ado (1 mmol/l). Both 1,3-dipropyl-8-cyclopentylxanthine (A1 blocker) and suramin (P2 blocker) partially blocked the ATP-induced inhibition of ICa, while their co-application nearly completely abolished the effect of ATP. ATP-gamma S (30 mumol/l) inhibited ISO-stimulated ICa significantly, and this inhibition was completely blocked by suramin. alpha, beta-Methylene-ADP, an inhibitor of hydrolysis of AMP to Ado, eliminated the suramin-resistant component of ICa inhibition by ATP. Pretreatment with pertussis toxin (PTX) abolished the ATP inhibition of ICa. Both intracellular dialysis with 8Br cAMP and the application of forskolin plus 3-isobutyl-1-methylxanthine also eliminated the effect of ATP.


CONCLUSIONS
Both P1 and P2 purinoceptors are involved in the ATP inhibition of ISO-stimulated ICa in rabbit atrial cells. The P1 stimulation by ATP results from hydrolysis of ATP to Ado. Both the P2- and the P1-mediated effects of ATP and Ado, respectively. involve a PTX-sensitive and cAMP-dependent pathway.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D051672:Shal Potassium Channels; D013498:Suramin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology