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.
Department of Medical Biochemistry, School of Medicine, Flinders University of South Australia, Adelaide.
K C
KC
Fernando
G J
GJ
Barritt
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002138:Calibration; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006873:Hydroquinones / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008345:Manganese / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D013050:Spectrometry, Fluorescence; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014667:Vasopressins / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D000975:Antioxidants; D006873:Hydroquinones; D013729:Terpenes; D010566:Virulence Factors, Bordetella; D014667:Vasopressins; D000804:Angiotensin II; C019359:2,5-di-tert-butylhydroquinone; D008345:Manganese; D004815:Epidermal Growth Factor; D019284:Thapsigargin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000252:Calcium-Transporting ATPases; D002118:Calcium