Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes.
Erythrocytes release ATP in response to exposure to the physiological stimulus of lowered oxygen (O(2)) tension as well as pharmacological activation of the prostacyclin receptor (IPR). ATP release in response to these stimuli requires activation of adenylyl cyclase, accumulation of cAMP, and activation of protein kinase A. The mechanism by which ATP, a highly charged anion, exits the erythrocyte in response to lowered O(2) tension or receptor-mediated IPR activation by iloprost is unknown. It was demonstrated previously that inhibiting pannexin 1 with carbenoxolone inhibits hypotonically induced ATP release from human erythrocytes. Here we demonstrate that three structurally dissimilar compounds known to inhibit pannexin 1 prevent ATP release in response to lowered O(2) tension but not to iloprost-induced ATP release. These results suggest that pannexin 1 is the conduit for ATP release from erythrocytes in response to lowered O(2) tension. However, the identity of the conduit for iloprost-induced ATP release remains unknown.
Sridharan
Meera
M
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA. sridham@slu.edu
Adderley
Shaquria P
SP
Bowles
Elizabeth A
EA
Egan
Terrance M
TM
Stephenson
Alan H
AH
Ellsworth
Mary L
ML
Sprague
Randy S
RS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D002229:Carbenoxolone / Q000494:pharmacology; D017630:Connexins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011339:Probenecid / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism
D017630:Connexins; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; C113936:PTGIR protein, human; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D016285:Iloprost; D002229:Carbenoxolone; D011339:Probenecid; D010100:Oxygen; D005905:Glyburide