G beta gamma transduces [Ca2+](i) oscillations and G alpha(q) 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 G beta gamma signal [Ca2+](i) oscillations and activation of G alpha(q) signal a sustained response during stimulation by a number of Ca2+-modilizing agonists. Thus, infusion of purified G beta gamma 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 G beta gamma, the beta-adrenergic receptor kinase fragment, and a mutated G alpha(i1G203A). These proteins, as well as an inhibitory antibody against G alpha(q/11), prevent [Ca2+](i) oscillations and the sustained response when applied before cell stimulation, possibly by preventing the dissociation of G(q) into its subunits. After cell stimulation and dissociation of G(q) into G beta gamma and G alpha(q), scavenging G beta gamma stabilized the sustained response and inhibited reassociation of the subunits on termination of cell stimulation with antagonist, whereas scavenging G alpha(q) inhibited the sustained response and uncovered the G beta gamma-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.