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-β-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+.
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Lerner, U.H., Brunius, G., Anduren, I. et al. Bradykinin induces a B2 receptor-mediated calcium signal linked to prostanoid formation in human gingival fibroblastsin vitro . Agents and Actions 37, 44–52 (1992). https://doi.org/10.1007/BF01987889
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DOI: https://doi.org/10.1007/BF01987889