PMID: 9539812May 16, 1998Paper

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Proceedings of the National Academy of Sciences of the United States of America
M BhatiaM L Steer

Abstract

Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis. To evaluate the role of substance P, pancreatitis was induced in mice that genetically lack NK1R by administration of 12 hourly injections of a supramaximally stimulating dose of the secretagogue caerulein. During pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil sequestration in the pancreas, and pancreatic acinar cell necrosis were significantly reduced in NK1R-/- mice when compared with wild-type NK1R+/+ animals. Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R-/- animals. These effects of NK1R deletion indicate that substance P, acting via NK1R, plays an important proinflammatory role in regulating the severity of acute pancreatitis and pancreatitis-associated lung injury.

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Citations

Jul 24, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Xiaoyun FangMin Yu
Jun 29, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Raina Devi RamnathMadhav Bhatia
Jun 23, 2010·Journal of Molecular Neuroscience : MN·Yusuke SakuraiAkemichi Baba
May 5, 2005·Journal of Autoimmunity·Solveig Persson-SjögrenSture Forsgren
Mar 10, 2004·Pharmacology, Biochemistry, and Behavior·Louis P Vera-Portocarrero, Karin N Westlund
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Jan 2, 2007·Pancreas·Yuk Cheung Chan, Po Sing Leung
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Feb 13, 2009·The Journal of Pharmacology and Experimental Therapeutics·Raina Devi RamnathMadhav Bhatia
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Apr 3, 2003·The Journal of Clinical Investigation·Mara Chavolla-CalderónJ Julio Pérez Fontán
Sep 21, 2000·The Journal of Clinical Investigation·W HalangkJ Deussing

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