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 α subunit genes were used to examine the role of the α 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, Gαq, Gα11, and Gα14 but not Gα15. Surprisingly, all parameters of Ca²⁺ signaling were identical in cells from wild type and four lines of mutant mice: 1) Gα11-/- , 2) Gα11-/-/Gα14-/-, 3) Gα14-/-/Gα15-/-, and 4) Gαq-/-/Gα15-/-. 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 Gαq, Gα11, and Gα14 promiscuously couple several receptors (m₃ muscarinic, bombesin, cholecystokinin, and α1 adrenergic) to effector proteins that activate both Ca²⁺ release from internal stores and Ca²⁺ entry.