Gbetagamma transduces [Ca2+]i oscillations and Galphaq a sustained response during stimulation of pancreatic acinar cells with [Ca2+]i-mobilizing agonists.
A central unresolved question in agonist-evoked [Ca2+]i signaling is the pathway by which [Ca2+]i oscillations and a sustained response are transduced. We show here that activation of Gbetagamma signal [Ca2+]i oscillations and activation of Galphaq signal a sustained response during stimulation by a number of Ca2+-mobilizing agonists. Thus, infusion of purified Gbetagamma into pancreatic acinar cells through a patch pipette evokes [Ca2+]i oscillations by Ca2+ release from internal stores, which were inhibited by two independent scavengers of Gbetagamma, the beta-adrenergic receptor kinase fragment, and a mutated Galphai1G203A. These proteins, as well as an inhibitory antibody against Galphaq/11, prevent [Ca2+]i oscillations and the sustained response when applied before cell stimulation, possibly by preventing the dissociation of Gq into its subunits. After cell stimulation and dissociation of Gq into Gbetagamma and Galphaq, scavenging Gbetagamma stabilized the sustained response and inhibited reassociation of the subunits on termination of cell stimulation with antagonist, whereas scavenging Galphaq inhibited the sustained response and uncovered the Gbetagamma-dependent oscillations. These findings provide a general mechanism by which Ca2+-mobilizing agonists can control the type of [Ca2+]i signal to be transduced to the cell interior.
Zeng
W
W
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Xu
X
X
Muallem
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000819:agonists / Q000378:metabolism*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
D002217:Carbachol; D019204:GTP-Binding Proteins; D002118:Calcium