Yamamoto T, Habuchi Y, Nishio M, Morikawa J, Tanaka H
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
Cardiovasc Res. 1999 Jan;41(1):166-74. doi: 10.1016/s0008-6363(98)00214-4.
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.
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.
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.
腺嘌呤化合物，包括三磷酸腺苷（ATP）和腺苷（Ado），通过P1（A1亚型）嘌呤受体对心肌发挥抑制作用。然而，ATP本身是P2嘌呤受体的强效激活剂。我们的目的是阐明P1和P2嘌呤受体在ATP对兔心房细胞L型钙电流（ICa）作用中的各自作用。
采用全细胞钳技术记录兔心脏单个心房细胞中的ICa。即使存在Ado（1 mmol/L），ATP（0.1 μmol/L - 3 mmol/L）对异丙肾上腺素（ISO，30 nmol/L）预刺激的ICa仍产生抑制作用。1,3 - 二丙基 - 8 - 环戊基黄嘌呤（A1阻滞剂）和苏拉明（P2阻滞剂）均部分阻断了ATP诱导的ICa抑制，而它们共同应用几乎完全消除了ATP的作用。ATP - γ - S（30 μmol/L）显著抑制ISO刺激的ICa，且这种抑制被苏拉明完全阻断。α，β - 亚甲基 - ADP，一种将AMP水解为Ado的抑制剂，消除了ATP对ICa抑制中苏拉明耐药的成分。用百日咳毒素（PTX）预处理消除了ATP对ICa的抑制。用8 - 溴 - cAMP进行细胞内透析以及应用福斯可林加3 - 异丁基 - 1 - 甲基黄嘌呤也消除了ATP的作用。
P1和P2嘌呤受体均参与了ATP对兔心房细胞中ISO刺激的ICa的抑制作用。ATP对P1的刺激源于ATP水解为Ado。ATP和Ado分别通过P2和P1介导的作用均涉及PTX敏感和cAMP依赖的途径。
