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VDAC is a Conduit for ATP Released from Human Red Blood Cells (RBCs) in Response to Prostacyclin (PGI2) Receptor (IPR) Activation
Author(s) -
Sridharan Meera,
Krantic Medina,
Richards Jennifer,
Dietrich Kristine,
Bowles Elizabeth,
Stephenson Alan H,
Ellsworth Mary L,
Sprague Randy S
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.635.5
RBCs release ATP in response to receptor‐mediated activation of the IPR or β‐adrenergic receptors (βARs) via distinct signaling pathways. Although each requires increases in cAMP, the final conduit for ATP release is unknown. Previously, we showed that pannexin 1 mediates ATP release when RBCs are exposed to low O 2 , but not in response to the IPR agonist, iloprost (ILO). Here we investigate the hypothesis that a voltage‐dependent anion channel (VDAC) is a conduit for ATP release in response to IPR activation. First, we confirmed that VDAC is expressed on human RBCs with Western analysis using two distinct anti‐VDAC antibodies. Next, washed human RBCs were incubated with iloprost (ILO, 1 μM), in the absence and presence of the VDAC inhibitor, Bcl‐x L BH4 4–23 (Bcl, 2 mg/ml). In the presence of Bcl, neither total ATP (luciferin/luciferase) nor ILO‐induced increases in cAMP (ELISA) were altered (n=6). In contrast, Bcl significantly inhibited ILO‐induced ATP release (n=6, P<0.01). Finally, neither Bcl (n=6) nor the pannexin 1 inhibitor, carbenoxolone (n=5), inhibited ATP release in response to incubation of erythrocytes with the βAR agonist, isoproterenol (1 μM). These results provide strong support for the hypothesis that, in human RBCs, VDAC is a conduit for ILO‐induced ATP release but not for ATP release associated with βAR activation. [Supported by NIH grant HL‐89094 and a Presidential Grant from SLU].