Salutary Effects of Tachykinin Receptor Antagonists in a Rat Model of Postoperative Ileus

Targeting tachykinin receptors for the treatment of functional gastrointestinal disorders with a focus on irritable bowel syndrome

“…Many studies, mainly in animals, have suggested that TKs are also implicated in modulation of inflammation and of inflammation‐induced alteration of motility and secretion in pathological gut conditions. Table reports the results of these studies …”

“…In animal models, the antagonism to NK1 and NK2 receptors has been demonstrated to reduce the gut inflammation and to reduce or reverse the inflammation‐induced hypo‐motility . In humans the maximal contractile response to TKs and their selective agonists has been demonstrated to be reduced in strips from patients with inflammatory bowel disorders (both ulcerative colitis and Crohn's disease) and diverticulitis, and this reduction has been attributed to a decreased number of receptors on smooth muscles induced by chronic exposure to TKs in inflammatory conditions …”

Distribution of the neurokinin‐1 receptor in equine intestinal smooth muscle

“…Tachykinins can therefore act directly on NK1R and NK2R on intestinal smooth muscle or indirectly by moderating the release of excitatory and inhibitory neurotransmitters following activation of NK1R, NK2R or NK3R on enteric neurons (Maggi et al 1997). Therapeutically, NKR antagonists have been used to alter motility in man and laboratory animals (Sanger 2004) and a combination of NK1R and NK2R antagonists was used successfully to treat experimental ileus in the rat (Ciechanownicz et al 2006). Substance P has been detected in enteric neurons and in enteroendocrine cells in the equine intestine Burns and Cummings 1993;Pearson 1994;Malone et al 1999Malone et al , 2000.…”

The novel CGRP receptor antagonist BIBN4096BS alleviates a postoperative intestinal inflammation and prevents postoperative ileus

“…Nevertheless, besides CGRP other neuropeptides coexist as preformed mediators and are likely to be released simultaneously with CGRP during IM. Some of them have also been investigated in experimental POI models, i.e., tachykinin, VIP and substance P . Of particular interest, substance P colocalizes with CGRP in DRG neurons, projecting to the murine jejunum and colon and substance P is known to induce proinflammatory cytokines via NK1 receptor in various cell types .…”