Su1937 Two Serine Protease Inhibitors, Nafamostat Mesylate and the Newly Developed SPIx, Decrease Post-Inflammatory Visceral Hypersensitivity in Rats

Ceuleers, Hannah; Segaert, Evelyn; Heirbaut, Jelena; Hanning, Nikita; Francque, Sven; Joossens, Jurgen; Meester, Ingrid De; Man, Joris De; Winter, Benedicte Y. De

doi:10.1016/s0016-5085(16)32036-4

Cited by 4 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an animal model for IBS, where the colonic permeability towards 51 Cr-EDTA was elevated and ZO-1 disrupted, treatment with camostat mesilate not only normalized the fecal protease activity but also the colonic permeability significantly improved and the ZO-1 protein levels were restored[ 89 ]. Nafamostat mesilate, that has shown beneficial effects on disease outcome in animal models of colitis[ 90 ], IBS[ 91 ], acute pancreatitis[ 92 ] and colorectal cancer[ 93 ], also seems to restore the intestinal barrier function. The addition of tryptase to the basolateral side of human colonic strips mounted in Ussing chambers increased the permeability proportional to the tryptase concentration.…”

Section: Serine Proteasesmentioning

confidence: 99%

Regulation of intestinal permeability: The role of proteases

Spaendonk

Ceuleers

Witters

et al. 2017

WJG

Self Cite

142

View full text Add to dashboard Cite

The gastrointestinal barrier is - with approximately 400 m2 - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.

show abstract

Section: Serine Proteasesmentioning

confidence: 99%

Regulation of intestinal permeability: The role of proteases

Spaendonk

Ceuleers

Witters

et al. 2017

WJG

Self Cite

142

View full text Add to dashboard Cite

show abstract

“…They used the supernatant of biopsies of IBS patients instead of fecal samples and apart from a decrease in visceral hypersensitivity, they also observed less sensitization of murine neurons after a pre-incubation with nafamostat mesilate. We recently demonstrated a positive effect of a single intraperitoneal injection of nafamostat mesilate in a trinitrobenzenesulfonic acid (TNBS)-induced rat model for both acute and post-inflammatory visceral hypersensitivity[66,67]. Furthermore, the newly developed serine protease inhibitor benzyl N-1-[bis(4-acetamidophenoxy)phosphoryl]-2-(4-carbamimidamidophenyl)ethyl-carbamate [UAMC-0050, patent WO2007045496 (A1)] showed anti-nociceptive properties as well, both in an acute and in a post-inflammatory setting[66,67].…”

Section: Proteases Protease-activated Receptors and Protease Inhibitmentioning

confidence: 99%

“…We recently demonstrated a positive effect of a single intraperitoneal injection of nafamostat mesilate in a trinitrobenzenesulfonic acid (TNBS)-induced rat model for both acute and post-inflammatory visceral hypersensitivity[66,67]. Furthermore, the newly developed serine protease inhibitor benzyl N-1-[bis(4-acetamidophenoxy)phosphoryl]-2-(4-carbamimidamidophenyl)ethyl-carbamate [UAMC-0050, patent WO2007045496 (A1)] showed anti-nociceptive properties as well, both in an acute and in a post-inflammatory setting[66,67]. Camostat mesilate, another serine protease inhibitor with structural properties similar to nafamostat mesilate showed analogous results.…”

Section: Proteases Protease-activated Receptors and Protease Inhibitmentioning

confidence: 99%

Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

Ceuleers

Spaendonk

Hanning

et al. 2016

WJG

Self Cite

View full text Add to dashboard Cite

Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.

show abstract

Abdominal Pain

Louwies

Meerveld

2022

Comprehensive Pharmacology

View full text Add to dashboard Cite

Su1937 Two Serine Protease Inhibitors, Nafamostat Mesylate and the Newly Developed SPIx, Decrease Post-Inflammatory Visceral Hypersensitivity in Rats

Cited by 4 publications

References 0 publications

Regulation of intestinal permeability: The role of proteases

Regulation of intestinal permeability: The role of proteases

Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

Abdominal Pain

Contact Info

Product

Resources

About