The role of protein kinase C isozymes in bombesin-stimulated gastrin release from human antral gastrin cells

Abstract

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 nM bombesin or 1 nM 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.