Substance P mediates inflammatory oedema in acute pancreatitis via activation of the neurokinin‐1 receptor in rats and mice
EF Grady, SK Yoshimi, J Maa… - British journal of …, 2000 - Wiley Online Library
EF Grady, SK Yoshimi, J Maa, D Valeroso, RK Vartanian, S Rahim, EH Kim, C Gerard…
British journal of pharmacology, 2000•Wiley Online LibraryPancreatic oedema occurs early in the development of acute pancreatitis, and the overall
extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is
released from sensory nerves, binds to the neurokinin‐1 receptor (NK1‐R) on endothelial
cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process
termed neurogenic inflammation. We sought to determine the importance of neurogenic
mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the …
extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is
released from sensory nerves, binds to the neurokinin‐1 receptor (NK1‐R) on endothelial
cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process
termed neurogenic inflammation. We sought to determine the importance of neurogenic
mechanisms in acute pancreatitis. Pancreatic plasma extravasation was measured using the …
- Pancreatic oedema occurs early in the development of acute pancreatitis, and the overall extent of fluid loss correlates with disease severity. The tachykinin substance P (SP) is released from sensory nerves, binds to the neurokinin‐1 receptor (NK1‐R) on endothelial cells and induces plasma extravasation, oedema, and neutrophil infiltration, a process termed neurogenic inflammation. We sought to determine the importance of neurogenic mechanisms in acute pancreatitis.
- Pancreatic plasma extravasation was measured using the intravascular tracers Evans blue and Monastral blue after administration of specific NK1‐R agonists/antagonists in rats and NK1‐R(+/+)/(−/−) mice. The effects of NK1‐R genetic deletion/antagonism on pancreatic plasma extravasation, amylase, myeloperoxidase (MPO), and histology in cerulein‐induced pancreatitis were characterized.
- In rats, both SP and the NK1‐R selective agonist [Sar9 Met(O2)11]SP stimulated pancreatic plasma extravasation, and this response was blocked by the NK1‐R antagonist CP 96,345. Selective agonists of the NK‐2 or NK‐3 receptors had no effect.
- In rats, cerulein stimulated pancreatic plasma extravasation and serum amylase. These responses were blocked by the NK1‐R antagonist CP 96,345.
- In wildtype mice, SP induced plasma extravasation while SP had no effect in NK1‐R knockout mice.
- In NK1‐R knockout mice, the effects of cerulein on pancreatic plasma extravasation and hyperamylasemia were reduced by 60%, and pancreatic MPO by 75%, as compared to wildtype animals.
- Neurogenic mechanisms of inflammation are important in the development of inflammatory oedema in acute interstitial pancreatitis.
British Journal of Pharmacology (2000) 130, 505–512; doi:10.1038/sj.bjp.0703343
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