Protease-activated receptor-1-induced calcium signaling in gingival fibroblasts is mediated by sarcoplasmic reticulum calcium release and extracellular calcium influx

Jiiang Huei Jeng, Chiu Po Chan, Hui Lin Wu, Yuan Soon Ho, Jang Jaer Lee, Chang Huei Liao, Yu Kaung Chang, Hsiao Hua Chang, Yi Jane Chen, Pey Jey Perng, Mei Chi Chang

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18 Citations (Scopus)


Thrombin is a serine protease activated during injury and inflammation. Thrombin and other proteases generated by periodontal pathogens affect the behavior of periodontal cells via activation of protease-activated receptors (PARs). We noted that thrombin and PAR-1 agonist peptide stimulated intracellular calcium levels ([Ca2+]i) of gingival fibroblasts (GF). This increase of [Ca2+]i was inhibited by EGTA and verapamil. U73122 and neomycin inhibited thrombin- and PAR-1-induced [Ca2+]i. Furthermore, 2-APB (75-100 μM, inositol triphosphate [IP3] receptor antagonist), thapsigargin (1 μM), SKF-96365 (200 μM) and W7 (50 and 100 μM) also suppressed the PAR-1- and thrombin-induced [Ca2+]i. However, H7 (100, 200 μM) and ryanodine showed little effects. Blocking Ca2+ efflux from mitochondria by CGP37157 (50, 100 μM) inhibited both thrombin- and PAR-1-induced [Ca2+]i. Thrombin induced the IP3 production of GF within 30-seconds of exposure, which was inhibited by U73122. These results indicate that mitochondrial calcium efflux and calcium-calmodulin pathways are related to thrombin and PAR-1 induced [Ca2+]i in GF. Thrombin-induced [Ca2+]i of GF is mainly due to PAR-1 activation, extracellular calcium influx via L-type calcium channel, PLC activation, then IP3 binding to IP3 receptor in sarcoplasmic reticulum, which leads to intracellular calcium release and subsequently alters cell membrane capacitative calcium entry.

Original languageEnglish
Pages (from-to)731-740
Number of pages10
JournalCellular Signalling
Issue number6
Publication statusPublished - Jun 2004



  • Calcium channel
  • Calcium mobilization
  • Calcium-calmodulin
  • Capacitative calcium entry
  • Gingival fibroblast
  • Inositol triphosphate receptor
  • Phospholipase C
  • Protease-activated receptors

ASJC Scopus subject areas

  • Cell Biology

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