C. Kimura et al., EFFECTS OF ACUTE GLUCOSE OVERLOAD ON HISTAMINE H-2 RECEPTOR-MEDIATED CA2-CELLS( MOBILIZATION IN BOVINE CEREBRAL ENDOTHELIAL), Diabetes, 47(1), 1998, pp. 104-112
[Ca2+](i) and whole-cell membrane current were measured in microvascul
ar endothelial cells from bovine brain. The effects of histamine on [C
a2+](i), were examined, and the acute effect of changing extracellular
glucose concentration on Ca2+ homeostasis was investigated. Applicati
on of 10 mu mol/l histamine evoked an initially transient and then sus
tained increase in [Ca2+](i) in normal Krebs solution, but only the tr
ansient component in Ca2+-free solution, thereby indicating that hista
mine mobilizes Ca2+ both from intracellular store sites and extracellu
lar space. The effects of histamine on [Ca2+](i) were inhibited by the
H-2 antagonist, ranitidine and cimetidine, but not by the H-1 antagon
ists, pyrilamine. Incubation of the cells for 2 h in solutions contain
ing low (1.1 and 2.3 mmol/l) or high (23 mmol/l) concentrations of glu
cose did not influence the resting level of [Ca2+](i). Treatment with
low concentrations of glucose did not impair histamine-induced Ca2+ mo
bilization. On the other hand, when histamine was applied to the cells
pretreated with 23 mmol/l glucose, it failed to mobilize Ca2+ from bo
th intracellular store sites and extracellular space. The effect of hi
stamine was mimicked by dibutyryl cyclic AMP, but glucose overload fai
led to inhibit this, suggesting that glucose overload inhibits H-2 rec
eptor-mediated cyclic AMP production. Glucose overload-induced impairm
ent of histamine action was reversed by pretreatment with staurosporin
e and calphostin C and mimicked by phorbol-12,13-dibutyrate, thereby s
uggesting the involvement of protein kinase C in the high glucose-indu
ced inhibition of Ca2+ mobilization. Whole-cell membrane current measu
rement showed that there was no difference in the membrane currents be
tween control and high glucose-treated cells. These results indicate t
hat in bovine brain microvascular endothelial cells, histamine induces
Ca2+ release from intracellular store sites and subsequent entry from
the extracellular space through the activation of H-2 receptors. Gluc
ose overload acutely inhibits histamine-induced Ca2+ mobilization by t
he activation of protein kinase C.