This hypothesis is supported by the fact that PAR2 can be activated by proteinases from pathogens such as dust mites or Porphyromonas gingivalis . PAR2 activation by pathogens would support a proinflammatory role for PAR2 in enteric infections and would suggest that PAR2 antagonists might be helpful in the treatment of enteric infections. In IBD models, however, activation of the ENS and further release of neuropeptides have been shown to be protective . Thus, in the setting of chronic intestinal inflammation, PAR2’induced ENS activation might have beneficial and protective effects. This hypothesis is further supported by the findings of Fiorucci and colleagues , who have observed that daily systemic treatment with a PAR2 agonist was protective in a model of trinitrobenzene sulfonic acid-induced colitis. The lack of readily available PAR2antagonists has hampered progress in this field. The availability of PAR2-deficient mice should help, in the very near future, to clarify this hypothesis.
Afferent sensory fibres of the ENS not only release inflammatory neuropeptides, but they also convey sensory data. One hypothesis is that activation of PARs, and particularly PAR2, on enteric afferent sensory fibres might also send a nociceptive signal to the central nervous system. It has been shown that subinflammatory doses of PAR2 agonists (PAR2-activating peptides but also trypsin and tryptase), when injected into the rat or mouse paw, provoked nociceptor activation at a spinal level, together with severe and prolonged hyperalgesia. Shop with best online pharmacy and find sale cialis tablets getting the most out of it.
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