Evidence from studies with hepatocyte suspensions that store-operated Ca²⁺ inflow requires a pertussis toxin-sensitive trimeric G-protein

The role of heterotrimeric GTP-binding proteins in the process of store-operated Ca²⁺ inflow in hepatocytes was investigated by testing the ability of pertussis toxin to inhibit thapsigargin- and 2,5-di-tert-butylhydroquinone (DBHQ)-induced bivalent cation inflow. Hepatocytes isolated from rats treated with pertussis toxin for 24 h exhibited markedly inhibited rates of both Ca²⁺ and Mn²⁺ inflow when these were stimulated by vasopressin, angiotension II, epidermal growth factor, thapsigargin and DBHQ. Pertussis toxin had little effect on the basal intracellular free Ca²⁺ concentration ([Ca²⁺](i)), basal rates of Ca²⁺ and Mn²⁺ inflow, the abilities of vasopressin, angiotensin II, thapsigargin and DBHQ to induce the release of Ca²⁺ from intracellular stores, and the maximum value of [Ca²⁺](i) reached following agonist-induced release of Ca²⁺ from intracellular stores. It is concluded that store-operated Ca²⁺ inflow in hepatocytes employs a slowly ADP-ribosylated trimeric GTP-binding protein and is the physiological mechanism, or one of the physiological mechanisms, by which vasopressin and angiotensin stimulate plasma membrane Ca²⁺ inflow in this cell type.