title: Bradykinin induces a B2 receptor-mediated calcium signal linked to prostanoid formation in human gingival fibroblasts in vitro.
abstract: The aim of the study was to determine the effect of bradykinin (BK) on the level of cytoplasmic-free Ca2+, [Ca2+]i, in human gingival fibroblasts and its relation to BK-induced prostanoid formation. BK, but not des-Arg9-BK, induced a significant rapid (within seconds) and transient increase in [Ca2+]i, that was not dependent on extracellular Ca2+. The stimulatory effect of BK was seen in concentrations at or above 10(-8) M, with the most pronounced effect at 10(-6) M. D-Arg0-Hyp3-Thi5,8-DPhe7-BK, a BK B2 receptor antagonist, but not des-Arg9-Leu8-BK, a BK B1 receptor antagonist, blocked BK-induced rise in [Ca2+]i. The BK B2 receptor antagonist also significantly reduced BK-induced PGE2 formation. When extracellular Ca2+ in the incubation medium was depleted, either by addition of EGTA or by omission of Ca2+ addition, BK still caused a significant stimulation of PGE2 formation. The calcium ionophores A23187 and ionomycin, similar to BK, caused a burst of PGE2 formation. The two phorbol esters phorbol 12,13-dibutyrate and 4-beta-phorbol-didecanoate positively amplified calcium ionophore A23187-induced PGE2 formation. The results indicate that BK-induced PGE2 formation in gingival fibroblasts is coupled to an increase in [Ca2+]i mediated by the BK B2 receptor, and which is independent of extracellular Ca2+.
authors.affiliation: Department of Oral Cell Biology, University of Umeå, Sweden.
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
authors.forename: G
authors.initials: G
authors.lastname: Brunius
authors.forename: I
authors.initials: I
authors.lastname: Andurén
authors.forename: P O
authors.initials: PO
authors.lastname: Berggren
authors.forename: L
authors.initials: L
authors.lastname: Juntti-Berggren
authors.forename: T
authors.initials: T
authors.lastname: Modéer
mesh_terms: D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003593:Cytoplasm / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium