Sprague R S, Ellsworth M L, Stephenson A H, Kleinhenz M E, Lonigro A J
Departments of Medicine and Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
Am J Physiol. 1998 Nov;275(5):H1726-32. doi: 10.1152/ajpheart.1998.275.5.H1726.
Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigate the hypothesis that the activity of the cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ATP binding cassette, is required for deformation-induced ATP release from RBCs. Incubation of rabbit RBCs with either of two inhibitors of CFTR activity, glibenclamide (10 microM) or niflumic acid (20 microM), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of CFTR to deformation-induced ATP release from human RBCs, cells from healthy humans, patients with cystic fibrosis (CF), or patients with chronic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mechanical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induced ATP release from rabbit and human RBCs requires CFTR activity, suggesting a previously unrecognized role for CFTR in the regulation of vascular resistance.
最近，有报道称兔和人的红细胞（RBCs）会因机械变形而释放ATP。在此，我们研究了以下假说：ATP结合盒成员囊性纤维化跨膜传导调节因子（CFTR）的活性是RBCs变形诱导ATP释放所必需的。用CFTR活性的两种抑制剂之一格列本脲（10微摩尔）或尼氟灭酸（20微摩尔）孵育兔RBCs，导致变形诱导的ATP释放受到抑制。为了证明CFTR对人RBCs变形诱导ATP释放的作用，研究了来自健康人、囊性纤维化（CF）患者或与CF无关的慢性阻塞性肺疾病（COPD）患者的细胞。健康人和COPD患者的RBCs在受到机械变形时会释放ATP。相比之下，CF患者的RBCs变形不会导致ATP释放。我们得出结论，兔和人RBCs变形诱导的ATP释放需要CFTR活性，这表明CFTR在调节血管阻力方面有一个以前未被认识到的作用。
