The enteric nervous system in inflammation and pain: par2 triggers enteric nerves (Part 2)

In: Enteric nervous system

13 Aug 2012

These results showed that the intestinal inflammation induced by PAR2 agonists is under neural control, and is affected by the release of neuropeptides such as substance P and CGRP. The release of substance P and CGRP, as a direct result of activation of PAR2 on ENS neurons, was not demonstrated in this study. Evidence supporting this idea include the facts that functional PAR2 has been identified on ENS neurons that also expressed substance P and CGRP, and that isolated sensory afferents can release substance P and CGRP upon direct application of PAR2agonists.

Taken together, these results showed that, upon PAR2 activation, the ENS releases neuropeptides (substance P and CGRP) that initiate neurogenic inflammation, characterized by edema and granulocyte infiltration (Figure 2).

Proteinase-activated receptor-2 (PAR2) activation causes neurogenic inflammation

Figure 2) Proteinase-activated receptor-2 (PAR2) activation causes neurogenic inflammation in the mouse colon. Upon PAR2 activation, the enteric nervous system releases substance P (SP) and calcitonin gene-related peptide (CGRP), two proinflammatory neuropeptides, which induce increased vascular permeability and vasodilation, thereby causing edema. PAR2-induced SP release, through the activation of neurokinin-1 receptors, is involved in granulocyte recruitment

An important step in understanding the role of PAR2 in the gut would be to investigate to what extent PAR2-induced ENS activation is associated with bowel disease. Because inflammation driven by enteric infections has been shown to be largely mediated by a neurogenic mechanism involving extrinsic sensory nerves, substance P and CGRP receptors , it could be hypothesized that pathogens release proteinases that activate PAR2 on enteric neurons, and that this activation leads to mucosal inflammation. You deserve best quality treatment that still does not cost too much money: you can get all that at the best pharmacy and purchase cialis here being sure you are making the best decision and it’s a wise one too.


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