Promiscuous coupling of receptors to Gq class alpha subunits and effector proteins in pancreatic and submandibular gland cells.

Mice with deficiencies in one or more Gq class alpha subunit genes were used to examine the role of the alpha subunit in regulating Ca2+ signaling in pancreatic and submandibular gland cells. Western blot analysis showed that these cells express three of the four Gq class subunits, Galphaq, Galpha11, and Galpha14 but not Galpha15. Surprisingly, all parameters of Ca2+ signaling were identical in cells from wild type and four lines of mutant mice: 1) Galpha11-/-, 2) Galpha11-/-/Galpha14-/-, 3) Galpha14-/-/Galpha15-/-, and 4) Galphaq-/-/Galpha15-/-. These parameters included the Kapp for several Gq class coupled receptors, induction of [Ca2+]i oscillations by weak stimulation, and a biphasic [Ca2+]i response by strong stimulation. Furthermore, Ca2+ release from internal stores and Ca2+ entry were not affected in cells from any of the mutant mice. We conclude that Galphaq, Galpha11, and Galpha14 promiscuously couple several receptors (m3 muscarinic, bombesin, cholecystokinin, and alpha1 adrenergic) to effector proteins that activate both Ca2+ release from internal stores and Ca2+ entry.