Neurotensin Partially Mediates the Monosodium Glutamate (MSG)‐Induced Peristaltic Reflex

Abstract

Activation of nutrient sensors throughout the gastrointestinal (GI) tract can affect both motility and secretory functions. Our recent studies have shown that monosodium glutamate (MSG) and the amino acid L-Cysteine can activate the nutrient sensing T1R1/T1R3 umami receptor and increase propulsive motility in the distal colon. Other groups have shown that activation of these receptors in the upper GI tract can lead to release of hormone and paracrine mediators from enteroendocrine cells (EECs). In this study we investigated the mechanism of MSG-induced increases in propulsive motility through the release of the paracrine mediator neurotensin (NT). We investigated MSG-induced release of NT in both a mouse enteroendocrine cell line, STC-1, and rat colon flat sheet preparation. In both STC-1 cells and guinea pig distal colon tissue T1R1/T1R3 receptors were co-localized to cells containing NT as assessed by immunohistochemistry. MSG induced NT release in both STC-1 cells and mucosal flat sheet preparations from rat colon. The NT release by MSG in rat colon was augmented by the addition of inosine-5'-monophosphate (IMP) suggesting that the effect was downstream of T1R1/T1R3 activation. MSG induced both the ascending contraction and descending relaxation components of the peristaltic reflex in rat colon, which was reduced by the addition of the NT1 receptor antagonist SR48692. The increased pellet propulsion velocity induced by MSG (132% of control) was reduced by the addition of the pan-NT receptor inhibitor SR142498 (115% of control). These results suggest that MSG-induced propulsive motility is partially mediated by the release of NT from EECs within the colonic mucosa. This research was supported by NIDDK grant DK034153 (JRG) and NIGMS grant GM093857.