title: Deformation-induced ATP release from red blood cells requires CFTR activity.
abstract: 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.
authors.affiliation: Departments of Medicine and Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Sprague
authors.forename: M L
authors.initials: ML
authors.lastname: Ellsworth
authors.forename: A H
authors.initials: AH
authors.lastname: Stephenson
authors.forename: M E
authors.initials: ME
authors.lastname: Kleinhenz
authors.forename: A J
authors.initials: AJ
authors.lastname: Lonigro
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D004912:Erythrocytes / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D011817:Rabbits; D013314:Stress, Mechanical
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate