title: Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury.
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.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bhatia
authors.forename: A K
authors.initials: AK
authors.lastname: Saluja
authors.forename: B
authors.initials: B
authors.lastname: Hofbauer
authors.forename: J L
authors.initials: JL
authors.lastname: Frossard
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: I
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Gerard
authors.forename: C
authors.initials: C
authors.lastname: Pothoulakis
authors.forename: M L
authors.initials: ML
authors.lastname: Steer
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide; D017353:Gene Deletion; D008168:Lung / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018040:Receptors, Neurokinin-1 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000502:physiology*
chemical_list: D018040:Receptors, Neurokinin-1; D013373:Substance P; D002108:Ceruletide; D000681:Amylases