title: Diamide decreases deformability of rabbit erythrocytes and attenuates low oxygen tension-induced ATP release.
abstract: Exposure of erythrocytes to reduced oxygen (O(2)) tension activates the heterotrimeric G-protein Gi, resulting in the accumulation of cyclic AMP (cAMP) and release of ATP. The mechanism by which exposure of erythrocytes to reduced O(2) tension activates Gi is not known. Here we investigate the hypothesis that, in rabbit erythrocytes, ATP release in response to exposure to reduced O(2) tension is linked to erythrocyte membrane deformability. If this hypothesis is correct, then decreasing the deformability of the erythrocyte membrane should decrease the release of ATP in response to reduced O(2) tension. We report that treating erythrocytes with diamide, a compound that decreases erythrocyte deformability, inhibits low O(2) tension-induced ATP release. Treating erythrocytes with diamide does not, however, interfere with cAMP accumulation or ATP release in response to a direct activator of Gi (mastoparan 7) or in response to receptor-mediated activation of Gs (the prostacyclin analog, iloprost). These results demonstrate that diamide (100 micromol/L) does not directly inhibit the signaling pathways for ATP release from rabbit erythrocytes and support the hypothesis that low O(2) tension-induced ATP release from these cells is linked to membrane deformability.
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA. sridham@slu.edu
authors.forename: Meera
authors.initials: M
authors.lastname: Sridharan
authors.forename: Randy S
authors.initials: RS
authors.lastname: Sprague
authors.forename: Shaquria P
authors.initials: SP
authors.lastname: Adderley
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bowles
authors.forename: Mary L
authors.initials: ML
authors.lastname: Ellsworth
authors.forename: Alan H
authors.initials: AH
authors.lastname: Stephenson
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood / Q000378:metabolism; D003958:Diamide / Q000378:metabolism; D004907:Erythrocyte Deformability / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D016285:Iloprost / Q000378:metabolism / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010100:Oxygen / Q000097:blood* / Q000378:metabolism*; D010455:Peptides; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D014862:Wasp Venoms
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D003958:Diamide; C017199:2',3'-dialdehyde ATP; C037500:mastoparan; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins; D016285:Iloprost; D010100:Oxygen