Substance P and bradykinin stimulate plasma extravasation in the mouse gastrointestinal tract and pancreas

Figini, Michela; Emanueli, Costanza; Grady, Eileen F.; Kirkwood, Kimberly S.; Payan, Donald G.; Ansel, John C.; Gérard, Craig; Geppetti, Pierangelo; Bunnett, Nigel W.

doi:10.1152/ajpgi.1997.272.4.g785

Cited by 67 publications

(88 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Capsaicin stimulates the release of SP and CGRP from primary sensory nerve endings in the gut (24) and thereby elicits an inflammatory response characterized by vasodilation and plasma extravasation (13). Consistently, intraveneous administration of SP in conscious rats stimulates the extravasation of plasma proteins in the duodenum, stomach, and pancreas (8,34). We have previously demonstrated that the lack of cutaneous capsaicin-induced plasma extravasation in Y1 Ϫ/Ϫ mice is caused by a failure of capsaicin-induced SP release (33).…”

Section: And Y1mentioning

confidence: 68%

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Hassani

Lucas

Rozell

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Neuropeptide Y (NPY), a 36-amino acid peptide, is widely expressed in the central and peripheral nervous system. NPY is involved in the regulation of several physiological processes, including energy balance, food intake, and nociception. Recently, we showed that activation of the NPY Y1 receptor is required for cutaneous neurogenic inflammation. Because neurogenic inflammation could participate in colitis, the aim of this study was to investigate the role of the NPY Y1 receptor in acute colitis using mice genetically deficient of NPY Y1 receptor. In addition, the Y1 receptor antagonist H409/22, was also investigated. Animals received 5% dextran sulfate sodium (DSS) in drinking water for 7 days. One group of animals also received the Y1 receptor antagonist, administered intraperitoneally twice daily. Disease activity was assessed daily for 7 days in all groups. DSS induced colitis in all animals resulting in weight loss, diarrhea, epithelial damage, crypt shortening, and inflammatory infiltration. However, clinical manifestation of the disease was markedly attenuated in Y1 null mutant mice as well as in mice receiving the Y1 antagonist. Histological analysis showed that tissue damage and ulceration were less severe in Y1-deficient animals. Consistent with the clinical and histological data, capsaicin-induced plasma extravasation was significantly reduced in the gut of Y1 null mutant animals compared with treated wild-type animals. These data indicate that NPY and Y1 receptor are involved in intestinal inflammation and suggest that inhibition of NPY Y1 receptor signaling may provide a novel therapeutic approach in the treatment of colonic inflammation. neurogenic inflammation; dextran sulfate sodium; in vivo animal models ULCERATIVE COLITIS AND CROHN'S disease constitute the two main forms of inflammatory bowel disease (IBD). This disease is characterized by a dysregulated immune response and chronic relapsing inflammation of the gastrointestinal (GI) tract, leading to diarrhea, hemoccult, abdominal pain, weight loss, and anemia.Despite intense research, the etiology of IBDs remains largely unknown. The development of IBD involves interactions among genetic, immunological, and environmental components (46). Other mediators implicated in the pathogenesis of colitis are neuropeptides released from enteric and sensory afferent neurons (37). These peptides have been shown to modulate different aspects of mucosal function, including blood flow and secretion, and may play a role in the recruitment of granulocytes and lymphocytes and in the modulation of mast cell activation (14,18).Stimulation and activation of capsaicin-sensitive sensory nerve endings produce an inflammatory response characterized by vasodilation and plasma extravasation (13). The inflammatory response is mediated by local release of sensory neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) (25). The inflammatory response, termed neurogenic inflammation, is well described in many peripheral organs including the skin, ai...

show abstract

Section: And Y1mentioning

confidence: 68%

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Hassani

Lucas

Rozell

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…Substance P is a major mediator of neurogenic inflammation in several tissues including skin (20,21), cardiovascular tissue (6, 9, 25), cephalic structures (13,17,26), respiratory tract (7,15,27), genitourinary tract (23,30), and gastrointestinal tract (12,16,25,32). NKA has also been shown to play an important role in neurogenic inflammation in several conditions.…”

Section: Discussionmentioning

confidence: 99%

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Bhatia

Slavin

Cao

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Impaired lung function in severe acute pancreatitis is the primary cause of morbidity and mortality in this condition. Preprotachykinin-A (PPT-A) gene products substance P and neurokinin (NK)-A have been shown to play important roles in neurogenic inflammation. Substance P acts primarily (but not exclusively) via the NK1 receptor. NKA acts primarily via the NK2 receptor. Earlier work has shown that knockout mice deficient in NK1 receptors are protected against acute pancreatitis and associated lung injury. NK1 receptors, however, bind other peptides in addition to substance P, not all of which are derived from the PPT-A gene. To examine the role of PPT-A gene products in acute pancreatitis, the effect of PPT-A gene deletion on the severity of acute pancreatitis and the associated lung injury was investigated. Deletion of PPT-A almost completely protected against acute pancreatitis-associated lung injury, with a partial protection against local pancreatic damage. These results show that PPT-A gene products are critical proinflammatory mediators in acute pancreatitis and the associated lung injury.

show abstract

“…We used Evans blue to measure extravasation of plasma proteins (4,15). Mice were anesthetized with xylazine (25 mg/kg i.m.)…”

Section: Methodsmentioning

confidence: 99%

“…SP mediates many aspects of neurogenic inflammation by interacting with the neurokinin-1 receptor (NK1R). Thus, SP interacts with the NK1R on endothelial cells of postcapillary venules in the airway and intestine to cause formation of gaps, which allows extravasation of plasma proteins (3,4).…”

mentioning

confidence: 99%

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Sturiale

Barbara

Qiu

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

162

112

View full text Add to dashboard Cite

Neurogenic inf lammation is regulated by sensory nerves and characterized by extravasation of plasma proteins and infiltration of neutrophils from post-capillary venules and arteriolar vasodilatation. Although it is well established that substance P (SP) interacts with the neurokinin 1 receptor (NK1R) to initiate neurogenic inf lammation, the mechanisms that terminate inf lammation are unknown. We examined whether neutral endopeptidase (NEP), a cellsurface enzyme that degrades SP in the extracellular f luid, terminates neurogenic inf lammation in the colon. In NEP knockout mice, the SP concentration in the colon was Ϸ2.5-fold higher than in wild-type mice, suggesting increased bioavailability of SP. The extravasation of Evans blue-labeled plasma proteins in the colon of knockout mice under basal conditions was Ϸ4-fold higher than in wild-type mice. This elevated plasma leak was attenuated by recombinant NEP or the NK1R antagonist SR140333, and is thus caused by diminished degradation of SP. To determine whether deletion of NEP predisposes mice to uncontrolled inf lammation, we compared dinitrobenzene sulfonic acid-induced colitis in wild-type and knockout mice. The severity of colitis, determined by macroscopic and histologic scoring and by myeloperoxidase activity, was markedly worse in knockout than wild-type mice after 3 and 7 days. The exacerbated inf lammation in knockout mice was prevented by recombinant NEP and SR140333. Thus, NEP maintains low levels of SP in the extracellular f luid under basal conditions and terminates its proinf lammatory effects. Because we have previously shown that intestinal inf lammation results in down-regulation of NEP and diminished degradation of SP, our present results suggest that defects in NEP expression contribute to uncontrolled inf lammation.

show abstract

Substance P and bradykinin stimulate plasma extravasation in the mouse gastrointestinal tract and pancreas

Cited by 67 publications

References 0 publications

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Attenuation of acute experimental colitis by preventing NPY Y1 receptor signaling

Preprotachykinin-A gene deletion protects mice against acute pancreatitis and associated lung injury

Neutral endopeptidase (EC 3.4.24.11) terminates colitis by degrading substance P

Contact Info

Product

Resources

About