Glucose overload attenuates histamine H2 receptor-mediated Ca2+ mobilization due to protein kinase C production in bovine cerebral endothelial cells.

Intracellular Ca2+ concentration ([Ca2+](i)) was measured in microvascular endothelial cells from bovine brain (BBEC). Effects of histamine on [Ca2+](i) was examined, and acute effect of changing extracellular glucose concentration on Ca2+ homeostasis was investigated. Application of 10muM histamine evoked an initial transient and following sustained increase in [Ca2+](i) in normal Krebs solution, but only the transient component in Ca2+ free solution, thereby indicating that histamine mobilizes Ca2+ both from intracellular store sites and extracellular space. The effects of histamine on [Ca2+](i) was inhibited by the H-2 antagonists, ranitidine and cimetidine, but not by the H-1 antagonist, pyrilamine. When histamine was applied to the cells pretreated with 23mM glucose for two hours, it failed to mobilize Ca2+ either from intracellular store site or extracellular space. Glucose overload-induced impairment of histamine action was reversed by pretreatment with staurosporine and calphostin C, and mimicked by phorbol-12,13-dibutyrate thereby suggesting the involvement of protein kinase C in the high glucose-induced inhibition of Ca2+ mobilization.