Histamine H-1 receptor-induced Ca2+ mobilization and prostaglandin E(2) release in human gingival fibroblasts - Possible role of receptor-operated Ca2+ influx

Stimulation of human gingival fibroblasts with histamine elicited an increase in the intracellular concentration of free calcium ([Ca2+](i)) and the formation of inositol 1,4,5-trisphosphate (InsP(3)) in a concentration- and time dependent manner. The histamine-induced increase in [Ca2+](i) was attenuated completely by chlorpheniramine, an H-1 antagonist, but not by cimetidine, an H-2 antagonist. The histamine-induced Ca2+ response consisted of an initial transient peak response and a subsequent sustained increase. The transient phase can be largely attributed to Ca2+ release from intracellular InsP(3)-sensitive stores since the increased [Ca2+](i) effect of histamine completely disappeared after depletion of intracellular Ca2+ stores with thapsigargin in the absence of extracellular Ca2+. The sustained phase was due to Ca2+ influx which was attenuated in the absence of extracellular Ca2+. The Ca2+ influx required the continuous binding of histamine to the receptor, since chlorpheniramine attenuated the increase in [Ca2+](i) observed when extracellular Ca2+ was re-applied to the cells after stimulation with histamine in the absence of extracellular Ca2+. Pretreatment with the Ca2+ channel blocker SK&F96365 inhibited the Ca2+ influx component, suggesting that histamine stimulates Ca2+ influx through an H-1 receptor-operated Ca2+ channel. Histamine also evoked a concentration- and time-dependent release of prostaglandin E(2) (PGE(2)). The histamine-evoked PGE(2) release was reduced markedly by exclusion of extracellular Ca2+ or pretreatment with SK&F96365 or an H-1 antagonist. These results indicate that histamine stimulates both the intracellular Ca2+ release from InsP, sensitive stores and the H-1 receptor-operated Ca2+ influx from extracellular sites. The increased [Ca2+](i) due to the Ca2+ influx causes PGE(2) release in human gingival fibroblasts.