Rabbit erythrocytes possess adenylyl cyclase type II that is activated by the heterotrimeric G proteins Gs and Gi.
Journal Title: Pharmacological Reports - Year 2005, Vol 57, Issue
Abstract
Adenosine triphosphate (ATP) release from rabbit erythrocytes occurs inresponse to deformation or reduced oxygen tension. A signal transduction pathway that relates these stimuli to ATP release has been proposed. This pathway includes the heterotrimeric G proteins, Gs and Gi, adenylyl cyclase, protein kinase A, and the cystic fibrosis transmembrane conductance regulator. Importantly, adenylyl cyclase types II, IV and VII have been reported to be activated by both Gs and Gi. Here, we demonstrate that rabbit erythrocytes possess an adenylyl cyclase subtype that is activated both by the alpha subunit and the betagamma subunit of Gs and Gi, respectively. Washed rabbit erythrocytes released ATP when exposed to the beta adrenergic receptor-mediated activator of Gs, isoproterenol (ISO, 10 muM,n = 8, p < 0.05) as well as in response to incubation with a direct activator of Gi, mastoparan 7 (MAS7, 10 muM, n = 12, p < 0.05). In contrast, an inactive mastoparan derivative, mastoparan 17 (MAS17, 10 muM, n = 6) did not stimulate ATP release. Importantly, incubation of washed rabbit erythrocytes with either isoprotenerol (ISO) (10 muM, n = 7) or MAS7 (10 muM, n = 11) resulted in increases in cyclic adenosinemonophosphate (cAMP) (p < 0.01). Western analysis was used to determine if an adenylyl cyclase capable of being activated by both Gs and Gi was a component of rabbit erythrocyte membranes. We identified adenylylcyclase type II with two antibodies generated against different epitopes of the protein. These results provide support for the hypothesis that, in rabbit erythrocytes, activation of either Gs or Gi results in the stimulation of adenylyl cyclase resulting in increases in cAMP leading, ultimately, to the release of ATP.
Authors and Affiliations
Randy Sprague, Elizabeth Bowles, Madelyn Stumpf, Gregory Ricketts, Alberto Freidman, Wei-Hsien Hou, Alan Stephenson, Andrew Lonigro
Keywords
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