PI 3-kinase- and ERK-MAPK-dependent mechanisms underlie Glucagon-Like Peptide-1-mediated activation of Sprague Dawley colonic myenteric neurons.

Ex-4 evoked neurally regulated suppression of rat colonic circular muscle activity. In myenteric neurons, the neurostimulatory effects of Ex-4 were dependent upon activation of PI 3-kinase and ERK-MAPK signaling cascades. No further change in circular muscle function was noted in the presence of CRF suggesting that stress does not impact on colonic function in health. Further studies in a model of IBS are needed to determine whether mechanisms are modified in the context of bowel dysfunction.