Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats

implications for the pathogenesis and prevention of ERCP-induced pancreatitis.

Zhi Jun He, John H. Winston, Tony E. Yusuf, Maria Adelaide Micci, Asem Elfert, Shu Yuan Xiao, Pankaj Jay Pasricha

Research output: Contribution to journalArticle

Abstract

INTRODUCTION: The neurogenic inflammatory mediator, substance P (SP), has been implicated in the pathogenesis of acute secretagogue-induced pancreatitis. We hypothesized that it may also play an important role in the development of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).AIMS Our aim was to evaluate the effectiveness of CP-96345, a NK1 receptor antagonist, in diminishing post-ERCP pancreatitis in a rat model. METHODS: The effects of CP-96345, when mixed with the contrast agent, were studied in a rat model of pancreatitis caused by retrograde contrast infusion. After 24 hours, histology, edema, and myeloperoxidase activity (MPO) of pancreas, plasma amylase, and NK1 receptor endocytosis in pancreatic acinar cells were evaluated. RESULTS: Intraductal contrast infusion caused increases in plasma amylase, edema, histologic grade, and MPO of pancreas, and NK1 receptor internalization in pancreatic acinar cells. The addition of CP-96345 to the infusate significantly reduced pancreatic edema, MPO activity, and the histologic grade of pancreatitis accompanied by a decrease in NK1 receptor internalization. CONCLUSIONS: When an NK1 receptor antagonist is delivered along with the contrast media there is significant reduction in the pancreatic inflammation caused by intraductal contrast infusion. These results provide some insight into the pathogenesis of ERCP induced pancreatitis as well as present novel pharmacological targets for its prevention.

Original languageEnglish (US)
JournalPancreas
Volume27
Issue number1
StatePublished - Jul 2003
Externally publishedYes

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Endoscopic Retrograde Cholangiopancreatography
Pancreatitis
Peroxidase
Edema
Acinar Cells
Amylases
Contrast Media
Pancreas
Substance P
Endocytosis
Histology
Pharmacology
Inflammation
CP 96345

ASJC Scopus subject areas

  • Gastroenterology
  • Endocrinology

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Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats : implications for the pathogenesis and prevention of ERCP-induced pancreatitis. / He, Zhi Jun; Winston, John H.; Yusuf, Tony E.; Micci, Maria Adelaide; Elfert, Asem; Xiao, Shu Yuan; Pasricha, Pankaj Jay.

In: Pancreas, Vol. 27, No. 1, 07.2003.

Research output: Contribution to journalArticle

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abstract = "INTRODUCTION: The neurogenic inflammatory mediator, substance P (SP), has been implicated in the pathogenesis of acute secretagogue-induced pancreatitis. We hypothesized that it may also play an important role in the development of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).AIMS Our aim was to evaluate the effectiveness of CP-96345, a NK1 receptor antagonist, in diminishing post-ERCP pancreatitis in a rat model. METHODS: The effects of CP-96345, when mixed with the contrast agent, were studied in a rat model of pancreatitis caused by retrograde contrast infusion. After 24 hours, histology, edema, and myeloperoxidase activity (MPO) of pancreas, plasma amylase, and NK1 receptor endocytosis in pancreatic acinar cells were evaluated. RESULTS: Intraductal contrast infusion caused increases in plasma amylase, edema, histologic grade, and MPO of pancreas, and NK1 receptor internalization in pancreatic acinar cells. The addition of CP-96345 to the infusate significantly reduced pancreatic edema, MPO activity, and the histologic grade of pancreatitis accompanied by a decrease in NK1 receptor internalization. CONCLUSIONS: When an NK1 receptor antagonist is delivered along with the contrast media there is significant reduction in the pancreatic inflammation caused by intraductal contrast infusion. These results provide some insight into the pathogenesis of ERCP induced pancreatitis as well as present novel pharmacological targets for its prevention.",
author = "He, {Zhi Jun} and Winston, {John H.} and Yusuf, {Tony E.} and Micci, {Maria Adelaide} and Asem Elfert and Xiao, {Shu Yuan} and Pasricha, {Pankaj Jay}",
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T1 - Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats

T2 - implications for the pathogenesis and prevention of ERCP-induced pancreatitis.

AU - He, Zhi Jun

AU - Winston, John H.

AU - Yusuf, Tony E.

AU - Micci, Maria Adelaide

AU - Elfert, Asem

AU - Xiao, Shu Yuan

AU - Pasricha, Pankaj Jay

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N2 - INTRODUCTION: The neurogenic inflammatory mediator, substance P (SP), has been implicated in the pathogenesis of acute secretagogue-induced pancreatitis. We hypothesized that it may also play an important role in the development of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).AIMS Our aim was to evaluate the effectiveness of CP-96345, a NK1 receptor antagonist, in diminishing post-ERCP pancreatitis in a rat model. METHODS: The effects of CP-96345, when mixed with the contrast agent, were studied in a rat model of pancreatitis caused by retrograde contrast infusion. After 24 hours, histology, edema, and myeloperoxidase activity (MPO) of pancreas, plasma amylase, and NK1 receptor endocytosis in pancreatic acinar cells were evaluated. RESULTS: Intraductal contrast infusion caused increases in plasma amylase, edema, histologic grade, and MPO of pancreas, and NK1 receptor internalization in pancreatic acinar cells. The addition of CP-96345 to the infusate significantly reduced pancreatic edema, MPO activity, and the histologic grade of pancreatitis accompanied by a decrease in NK1 receptor internalization. CONCLUSIONS: When an NK1 receptor antagonist is delivered along with the contrast media there is significant reduction in the pancreatic inflammation caused by intraductal contrast infusion. These results provide some insight into the pathogenesis of ERCP induced pancreatitis as well as present novel pharmacological targets for its prevention.

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