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

Madhav Bhatia, Ashok K. Saluja, Bernd Hofbauer, Jean Louis Frossard, Hong Sik Lee, Ignazio Castagliuolo, Chi Chung Wang, Norma Gerard, Charalabos Pothoulakis, Michael L. Steer

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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.

Original languageEnglish
Pages (from-to)4760-4765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number8
DOIs
Publication statusPublished - 1998 Apr 14
Externally publishedYes

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Neurokinin-1 Receptors
Lung Injury
Substance P
Pancreatitis
Acinar Cells
Pancreas
Neutrophils
Hyperamylasemia
Ceruletide
Capillary Permeability
Necrosis
Lung
Injections

ASJC Scopus subject areas

  • General

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Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. / Bhatia, Madhav; Saluja, Ashok K.; Hofbauer, Bernd; Frossard, Jean Louis; Lee, Hong Sik; Castagliuolo, Ignazio; Wang, Chi Chung; Gerard, Norma; Pothoulakis, Charalabos; Steer, Michael L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 8, 14.04.1998, p. 4760-4765.

Research output: Contribution to journalArticle

Bhatia, M, Saluja, AK, Hofbauer, B, Frossard, JL, Lee, HS, Castagliuolo, I, Wang, CC, Gerard, N, Pothoulakis, C & Steer, ML 1998, '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, vol. 95, no. 8, pp. 4760-4765. https://doi.org/10.1073/pnas.95.8.4760
Bhatia, Madhav ; Saluja, Ashok K. ; Hofbauer, Bernd ; Frossard, Jean Louis ; Lee, Hong Sik ; Castagliuolo, Ignazio ; Wang, Chi Chung ; Gerard, Norma ; Pothoulakis, Charalabos ; Steer, Michael L. / Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 8. pp. 4760-4765.
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