Although the presence of PARj, PAR2 and PAR4 was not clearly established, a study by Gao et al suggested that those receptors act on neurons that regulate enteric motor function in the guinea pig small intestine.
This large expression of PARs strongly suggests that they play a crucial role in the physiology and pathophysiology of the ENS. Among the functions of the ENS, it appears that pro-teinases and PARs are especially likely to regulate inflammation and pain.
It is known that all the hallmarks of inflammation – swelling, increased blood flow and granulocyte infiltration – are induced by exposure of various tissues (paw, airways, skin, etc) to PAR2 agonists . Because proteinases that are able to activate PAR2 (such as trypsin and mast cell tryptase) are particularly abundant in the gut of patients with inflammatory bowel diseases (IBD) , we hypothesized that high concentrations of proteinases in the lumen of the gut might induce intestinal inflammation.
We have shown that, in the rat colon, the intracolonic injection of a selective PAR2 agonist (PAR2-activating peptide), as well as of trypsin and mast cell tryptase, caused edema, granulocyte infiltration and intestinal barrier breakdown, as demonstrated by bacterial translocation from the gut to peripheral organs . Furthermore, we have shown that this PAR2 agonist-mediated colitis could be inhibited by a pretreatment with capsaicin, a neurotoxin that depletes sensory neurons of their neuropeptide content, or pretreatment with NK-1 or CGRP receptor antagonists. You can soon shop with a nice pharmacy offering cialis super active online pharmacy buy now to benefit more.
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