Bradykinin induces a B2 receptor-mediated calcium signal linked to prostanoid formation in human gingival fibroblasts in vitro.
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+.
Lerner
U H
UH
Department of Oral Cell Biology, University of Umeå, Sweden.
Brunius
G
G
Andurén
I
I
Berggren
P O
PO
Juntti-Berggren
L
L
Modéer
T
T
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
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium