Promiscuous coupling of receptors to Gq class α 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 a 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, G alpha q, G alpha 11, and G alpha 14 but not G alpha 15. Surprisingly, all parameters of Ca2+ signaling were identical in cells from wild type and four lines of mutant mice: 1) G alpha 11-/-, 2) G alpha 11-/-/G alpha 14-/-, 3) G alpha 14-/-/Ga15-/-, and 4) G alpha q-/-/G alpha 15-/-. These parameters included the K-app 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 G alpha q, G alpha 11, and G alpha 14 promiscuously couple several receptors (m(3) muscarinic, bombesin, cholecystokinin, and alpha 1 adrenergic) to effector proteins that activate both Ca2+ release from internal stores and Ca2+ entry.