OBJECTIVES: We tested the hypothesis that leukotriene B4 (LTB4) mediates pancreatic inflammation in rats via activation of the transient receptor potential vanilloid 1 (TRPV1). METHODS: Leukotriene B4 or a vehicle was administered to adult rats via celiac axis injection after pretreatment with the TRPV1 antagonist, capsazepine, or vehicle, and the severity of subsequent pancreatitis was assessed by measuring pancreatic edema, myeloperoxidase (MPO) activity, and histological grading. In a second experiment, acute pancreatitis was induced by common pancreaticobiliary duct ligation. Six hours after surgery, pancreatic tissue levels of LTB4 were determined by enzyme-linked immunosorbent assay. Also, the effects of inhibition of LTB4 biosynthesis by pretreatment with the 5-lipoxygenase-activating peptide inhibitor, MK-886, were determined. RESULTS: Celiac axis administration of LTB4 significantly increased pancreatic edema and MPO activity, and produced histological evidence of pancreatic edema, neutrophil infiltration, and necrosis. Capsazepine pretreatment significantly reduced all inflammatory parameters in LTB4-induced pancreatitis. Pancreatic tissue levels of LTB4 were significantly elevated in rats that underwent common pancreaticobiliary duct ligation compared with control rats. MK-886 pretreatment significantly inhibited pancreatic edema, histological damage, and pancreatic MPO concentrations. CONCLUSIONS: Common pancreaticobiliary duct obstruction causes an increase in pancreatic LTB4 concentrations that in turn mediates activation of TRPV1 resulting in acute pancreatitis.
OBJECTIVES: We tested the hypothesis that leukotriene B4 (LTB4) mediates pancreatic inflammation in rats via activation of the transient receptor potential vanilloid 1 (TRPV1). METHODS:Leukotriene B4 or a vehicle was administered to adult rats via celiac axis injection after pretreatment with the TRPV1 antagonist, capsazepine, or vehicle, and the severity of subsequent pancreatitis was assessed by measuring pancreatic edema, myeloperoxidase (MPO) activity, and histological grading. In a second experiment, acute pancreatitis was induced by common pancreaticobiliary duct ligation. Six hours after surgery, pancreatic tissue levels of LTB4 were determined by enzyme-linked immunosorbent assay. Also, the effects of inhibition of LTB4 biosynthesis by pretreatment with the 5-lipoxygenase-activating peptide inhibitor, MK-886, were determined. RESULTS: Celiac axis administration of LTB4 significantly increased pancreatic edema and MPO activity, and produced histological evidence of pancreatic edema, neutrophil infiltration, and necrosis. Capsazepine pretreatment significantly reduced all inflammatory parameters in LTB4-induced pancreatitis. Pancreatic tissue levels of LTB4 were significantly elevated in rats that underwent common pancreaticobiliary duct ligation compared with control rats. MK-886 pretreatment significantly inhibited pancreatic edema, histological damage, and pancreaticMPO concentrations. CONCLUSIONS: Common pancreaticobiliary duct obstruction causes an increase in pancreaticLTB4 concentrations that in turn mediates activation of TRPV1 resulting in acute pancreatitis.
Authors: J D Nathan; A A Patel; D C McVey; J E Thomas; V Prpic; S R Vigna; R A Liddle Journal: Am J Physiol Gastrointest Liver Physiol Date: 2001-11 Impact factor: 4.052
Authors: L Hanus; S Abu-Lafi; E Fride; A Breuer; Z Vogel; D E Shalev; I Kustanovich; R Mechoulam Journal: Proc Natl Acad Sci U S A Date: 2001-03-20 Impact factor: 11.205
Authors: Jaimie D Nathan; Ruth Y Peng; Yu Wang; Douglas C McVey; Steven R Vigna; Rodger A Liddle Journal: Am J Physiol Gastrointest Liver Physiol Date: 2002-10 Impact factor: 4.052
Authors: Tessa ten Hove; Paul Drillenburg; Jan Wijnholds; Anje A Te Velde; Sander J H van Deventer Journal: Dig Dis Sci Date: 2002-09 Impact factor: 3.199
Authors: Susan M Huang; Tiziana Bisogno; Marcello Trevisani; Abdulmonem Al-Hayani; Luciano De Petrocellis; Filomena Fezza; Michele Tognetto; Timothy J Petros; Jocelyn F Krey; Constance J Chu; Jeffrey D Miller; Stephen N Davies; Pierangelo Geppetti; J Michael Walker; Vincenzo Di Marzo Journal: Proc Natl Acad Sci U S A Date: 2002-06-11 Impact factor: 11.205
Authors: Jami L Saloman; Kathryn M Albers; Zobeida Cruz-Monserrate; Brian M Davis; Mouad Edderkaoui; Guido Eibl; Ariel Y Epouhe; Jeremy Y Gedeon; Fred S Gorelick; Paul J Grippo; Guy E Groblewski; Sohail Z Husain; Keane K Y Lai; Stephen J Pandol; Aliye Uc; Li Wen; David C Whitcomb Journal: Pancreas Date: 2019-07 Impact factor: 3.327
Authors: Anna N Bukiya; Jacob McMillan; Jianxi Liu; Bangalore Shivakumar; Abby L Parrill; Alex M Dopico Journal: J Biol Chem Date: 2014-11-04 Impact factor: 5.157
Authors: Song Han; Ella W Englander; Guillermo A Gomez; Judith F Aronson; Cristiana Rastellini; R P Garofalo; Deepthi Kolli; Thomas Quertermous; Ramendra Kundu; George H Greeley Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-05-16 Impact factor: 4.052