Acinar Cell Production of Leukotriene B4 Contributes to Development of Neurogenic Pancreatitis in Mice

Cellular and Molecular Gastroenterology and Hepatology
Rafiq A ShahidR A Liddle

Abstract

In the pancreas, activation of primary sensory nerves through the transient receptor potential ion channel TRPV1 contributes to the early stages of development of pancreatitis. Little is known about the mechanism by which this occurs. We investigated whether leukotriene B4 (LTB4) is an endogenous agonist of TRPV1 and mediates pancreatitis. Acute inflammation was induced in the pancreata of Trpv1(-/-) mice and their wild-type littermates by retrograde infusion of the main pancreatic duct with 2% sodium taurocholate (NaT) or intraperitoneal injections of caerulein. Mice were also given injections of resiniferatoxin (an excitotoxin that desensitizes TRPV1) or MK886 (a drug that inhibits LTB4 biosynthesis). Pancreatic tissues and plasma were collected and analyzed. Retrograde perfusion of the main pancreatic ducts of wild-type mice with NaT caused severe acute pancreatitis; severity was reduced by co-administration of resiniferatoxin. Trpv1(-/-) mice developed a less severe pancreatitis following NaT administration than controls. Administration of MK886 before perfusion with NaT also significantly reduced the severity of pancreatitis in wild-type mice. Pancreatic tissues from mice given NaT had a marked increase in the level of 5-l...Continue Reading

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Citations

Aug 23, 2019·American Journal of Physiology. Gastrointestinal and Liver Physiology·Ajay DixitAshok K Saluja
May 2, 2018·Nature Communications·Joelle M-J RomacRodger A Liddle
Nov 17, 2020·Frontiers in Immunology·Harold A SilvermanEric H Chang

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