Lippton H L, Hao Q, Hauth T, Hyman A
Department of Internal Medicine, Louisiana State University Medical School, New Orleans.
Am J Physiol. 1992 Mar;262(3 Pt 2):H926-9. doi: 10.1152/ajpheart.1992.262.3.H926.
The purpose of the present study was to investigate the contribution of pertussis toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular response to adenosine and ATP in the intact cat under conditions of controlled pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP increased lobar arterial pressure in a dose-dependent manner. The pulmonary vasoconstrictor response to adenosine was abolished by BW 1433U, a specific purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708, a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the pulmonary vasoconstrictor response to adenosine depends on activation of P1 purinergic receptors coupled to PTX-sensitive G proteins and subsequent metabolism of liberated arachidonic acid to form TxA2. Because each blocking agent studied produced similar reductions in the pulmonary vasoconstrictor response to ATP without altering the pulmonary vasoconstrictor response to beta-tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed, in part, by hydrolysis to adenosine. Moreover, the present study suggests that both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x purinoceptors receptors that are independent of PTX-insensitive G proteins mediate the pulmonary vasoconstrictor response to ATP in vivo.
本研究的目的是在肺血流量和左心房压力得到控制的条件下，研究百日咳毒素（PTX）敏感的鸟嘌呤核苷酸（G）蛋白在完整猫肺血管对腺苷和ATP反应中的作用。腺苷、ATP和β-τ-ATP以剂量依赖的方式升高叶动脉压。BW 1433U（一种特异性嘌呤能受体（P1）抑制剂）、PTX预处理、吲哚美辛和血栓素A2（TxA2）受体拮抗剂ONO 3708可消除肺血管对腺苷的收缩反应。这些数据表明，肺血管对腺苷的收缩反应取决于与PTX敏感的G蛋白偶联的P1嘌呤能受体的激活以及游离花生四烯酸随后代谢形成TxA2。由于所研究的每种阻断剂对肺血管对ATP的收缩反应产生相似程度的降低，而不改变肺血管对β-τ-ATP的收缩反应，因此目前的数据表明，ATP部分地通过水解为腺苷来收缩肺血管床。此外，本研究表明，与PTX敏感的G蛋白相关的A1嘌呤受体以及与不依赖于PTX不敏感G蛋白的P2x嘌呤受体均介导体内肺血管对ATP的收缩反应。
