Open AccessActivation of neurokinin‐1 receptors up‐regulates substance P and neurokinin‐1 receptor expression in murine pancreatic acinar cells
Author(s) -
Koh YungHua,
Moochhala Shabbir,
Bhatia Madhav
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2011.01475.x
Subject(s) - substance p , tachykinin receptor 1 , receptor , medicine , endocrinology , rottlerin , agonist , acinar cell , tachykinin receptor , mapk/erk pathway , acute pancreatitis , pancreas , biology , chemistry , microbiology and biotechnology , neuropeptide , signal transduction , protein kinase c
Acute pancreatitis (AP) has been associated with an up‐regulation of substance P (SP) and neurokinin‐1 receptor (NK1R) in the pancreas. Increased SP‐NK1R interaction was suggested to be pro‐inflammatory during AP. Previously, we showed that caerulein treatment increased SP/NK1R expression in mouse pancreatic acinar cells, but the effect of SP treatment was not evaluated. Pancreatic acinar cells were obtained from pancreas of male swiss mice (25–30 g). We measured mRNA expression of preprotachykinin‐A (PPTA) and NK1R following treatment of SP (10 −6 M). SP treatment increased PPTA and NK1R expression in isolated pancreatic acinar cells, which was abolished by pretreatment of a selective NK1R antagonist, CP96,345. SP also time dependently increased protein expression of NK1R. Treatment of cells with a specific NK1R agonist, GR73,632, up‐regulated SP protein levels in the cells. Using previously established concentrations, pre‐treatment of pancreatic acinar cells with Gö6976 (10 nM), rottlerin (5 μM), PD98059 (30 μM), SP600125 (30 μM) or Bay11‐7082 (30 μM) significantly inhibited up‐regulation of SP and NK1R. These observations suggested that the PKC‐ERK/JNK‐NF‐κB pathway is necessary for the modulation of expression levels. In comparison, pre‐treatment of CP96,345 reversed gene expression in SP‐induced cells, but not in caerulein‐treated cells. Overall, the findings in this study suggested a possible auto‐regulatory mechanism of SP/NK1R expression in mouse pancreatic acinar cells, via activation of NK1R. Elevated SP levels during AP might increase the occurrence of a positive feedback loop that contributes to abnormally high expression of SP and NK1R.