The role of protein kinase C isozymes in bombesin-stimulated gastrin release from human antral gastrin cells.
Two of the most effective stimuli of gastrin release from human antral G cells are bombesin and phorbol esters. Both agonists result in activation of the protein kinase C family of isozymes, however, the exact contribution of protein kinase C to the resultant release of gastrin has been difficult to assess, possibly due to the presence of multiple protein kinase C isozymes in the G cells. The results of the present study demonstrated that the human antral G cells expressed 6 protein kinase C isozymes alpha, gamma, theta, epsilon, zeta, and mu. Of these protein kinase C, gamma and theta were translocated by stimulation of the cells by either 10 nM bombesin or 1 nM phorbol ester. Inhibition of protein kinase Cmu (localized to the Golgi complex) did not decrease bombesin-stimulated gastrin release indicating that this isozyme was not involved in the secretory process. The use of selective antagonists of the calcium-sensitive conventional protein kinase C subgroup resulted in an increase in bombesin-stimulated gastrin release and indicated that protein kinase Cgamma was involved in the desensitization of the bombesin response.
Moore
E D
ED
Department of Physiology, University of British Columbia, Vancouver V6T 1Z3, Canada.
Ring
M
M
Scriven
D R
DR
Smith
V C
VC
Meloche
R M
RM
Buchan
A M
AM
D000328:Adult; D001692:Biological Transport; D001839:Bombesin / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D005260:Female; D019863:Gastrin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011706:Pyloric Antrum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002227:Carbazoles; D005755:Gastrins; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D009281:Naphthalenes; C081021:Go 6976; D011493:Protein Kinase C; C058819:calphostin C; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin