DEFORMATION-INDUCED ATP RELEASE FROM RED-BLOOD-CELLS REQUIRES CFTR ACTIVITY

Recently, it was reported that rabbit and human red blood cells (RBCs) release ATP in response to mechanical deformation. Here we investigat e the hypothesis that the activity of the cystic fibrosis transmembran e 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, glibenc lamide (10 mu M) or niflumic acid (20 mu M), resulted in inhibition of deformation-induced ATP release. To demonstrate the contribution of C FTR to deformation-induced ATP release from human RBCs, cells from hea lthy humans, patients with cystic fibrosis (CF), or patients with chro nic obstructive lung disease (COPD) unrelated to CF were studied. RBCs of healthy humans and COPD patients released ATP in response to mecha nical deformation. In contrast, deformation of RBCs from patients with CF did not result in ATP release. We conclude that deformation-induce d ATP release from rabbit and human RBCs requires CFTR activity, sugge sting a previously unrecognized role for CFTR in the regulation of vas cular resistance.