The Role of Protein Kinase C Isozymes in Bombesin-stimulated Gastrin Release from Human Antral Gastrin Cells

• Published in: The Journal of biological chemistry 1999-08, Vol.274 (32), p.22493-22501
• Main Authors: Moore, E D, Ring, M, Scriven, D R, Smith, V C, Meloche, R M, Buchan, A M
• Format: Article
• Language: English
• Subjects: Adult; Biological Transport; Bombesin - pharmacology; Carbazoles - pharmacology; Female; Gastrin-Secreting Cells - drug effects; Gastrin-Secreting Cells - metabolism; Gastrins - metabolism; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Indoles - pharmacology; Isoenzymes - metabolism; Male; Maleimides - pharmacology; Naphthalenes - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Pyloric Antrum - cytology; Pyloric Antrum - drug effects; Pyloric Antrum - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.32.22493

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 α, γ, θ, ε, ζ, and μ. Of these protein kinase C, γ and θ were translocated by stimulation of the cells by either 10 n m bombesin or 1 n m phorbol ester. Inhibition of protein kinase Cμ (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 Cγ was involved in the desensitization of the bombesin response.