title: Histamine H1 receptor-induced Ca2+ mobilization and prostaglandin E2 release in human gingival fibroblasts. Possible role of receptor-operated Ca2+ influx.
abstract: 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 (InsP3) in a concentration- and time-dependent manner. The histamine-induced increase in [Ca2+]i was attenuated completely by chlorpheniramine, an H1 antagonist, but not by cimetidine, an H2 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 InsP3-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 H1 receptor-operated Ca2+ channel. Histamine also evoked a concentration- and time-dependent release of prostaglandin E2 (PGE2). The histamine-evoked PGE2 release was reduced markedly by exclusion of extracellular Ca2+ or pretreatment with SK&F96365 or an H1 antagonist. These results indicate that histamine stimulates both the intracellular Ca2+ release from InsP3-sensitive stores and the H1 receptor-operated Ca2+ influx from extracellular sites. The increased [Ca2+]i due to the Ca2+ influx causes PGE2 release in human gingival fibroblasts.
authors.affiliation: Department of Periodontology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Niisato
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.forename: S
authors.initials: S
authors.lastname: Furuyama
authors.forename: H
authors.initials: H
authors.lastname: Sugiya
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism*; D005881:Gingiva / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013997:Time Factors
chemical_list: D011969:Receptors, Histamine H1; D006632:Histamine; D015232:Dinoprostone; D002118:Calcium