Gβγ transduces [Ca2+](i) oscillations and Gα(q) a sustained response during stimulation of pancreatic acinar cells with [Ca2+](i)- mobilizing agonists

Abstract

A central unresolved question in agonist-evoked [Ca-1](i) signaling is the pathway by which [Ca-1](i) oscillations and a sustained response are transduced. We show here that activation of Gβγ signal [Ca-1](i) oscillations and activation of Gα(q) signal a sustained response during stimulation by a number of Ca2+-mobilizing agonists. Thus, infusion of purified Gβγ into pancreatic acinar cells through a patch pipette evokes [Ca-1](i) oscillations by Ca2+ release from internal stores, which were inhibited by two independent scavengers of Gβγ, the β-adrenergic receptor kinase fragment, and a mutated Gα(11G203A). These proteins, as well as an inhibitory antibody against Gα(q/11), prevent [Ca-1](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 Gβγ and Gα(q), scavenging Gβγ stabilized the sustained response and inhibited reassociation of the subunits on termination of cell stimulation with antagonist, whereas scavenging Gα(q) inhibited the sustained response and uncovered the Gβγ-dependent oscillations. These findings provide a general mechanism by which Ca2+- mobilizing agonists can control the type of [Ca-1](i) signal to be transduced to the cell interior.