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Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury
Open accessAbstract
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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Cited by
Hydrogen sulfide is a novel mediator of lipopolysaccharide‐induced inflammation in the mouse
Li, L., Bhatia, M., Zhu, Y. Z., Zhu, Y. C., Ramnath, R. D., Wang, Z. J., Anuar, F. B. M., Whiteman, M., Salto‐Tellez, M., & Moore, P. K. (2005) · The FASEB Journal · doi:10.1096/fj.04-3583fje · Cited by 773
Self-citationKalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2016) · Comprehensive Physiology · doi:10.1002/cphy.c160006 · Cited by 718
Acute Pancreatitis: Bench to the Bedside
Pandol, S. J., Saluja, A. K., Imrie, C. W., & Banks, P. A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.055 · Cited by 677
Self-citationSteinhoff, M. S., von Mentzer, B., Geppetti, P., Pothoulakis, C., & Bunnett, N. W. (2014) · Physiological Reviews · doi:10.1152/physrev.00031.2013 · Cited by 628
Self-citationPathophysiology of acute pancreatitis
Bhatia, M., Wong, F. L., Cao, Y., Lau, H. Y., Huang, J., Puneet, P., & Chevali, L. (2005) · Pancreatology · doi:10.1159/000085265 · Cited by 544
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Metadata
- Authors
- Bhatia, M., Saluja, A. K., Hofbauer, B., Frossard, J.-L., Lee, H. S., Castagliuolo, I., Wang, C.-C., Gerard, N., Pothoulakis, C., & Steer, M. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-04-14
- Volume
- 95
- Issue
- 8
- Pages
- 4760-4765
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2105929254
- Cited by
- 292
- References
- 0
- FWCI
- 14.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Bhatia, M., Saluja, A. K., Hofbauer, B., Frossard, J.-L., Lee, H. S., Castagliuolo, I., Wang, C.-C., Gerard, N., Pothoulakis, C., & Steer, M. L. (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. https://doi.org/10.1073/pnas.95.8.4760
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