Taste-Signaling Proteins Are Coexpressed in Solitary Intestinal Epithelial Cells

Abstract

The taste system, made up of taste receptor cells clustered in taste buds at the surface of the tongue and the soft palate, plays a key role in the decision to ingest or reject food and thereby is essential in protecting organisms against harmful toxins and in selecting the most appropriate nutrients. To determine if a similar chemosensory system exists in the gastrointestinal tract, we used immunohistochemistry and real-time polymerase chain reaction (PCR) to investigate which taste-signaling molecules are expressed in the intestinal mucosa. The PCR data showed that T1r1, T1r2, T1r3, alpha-gustducin, phospholipase Cbeta2 (PLCbeta2), and Trpm5 are expressed in the stomach, small intestine, and colon of mice and humans, with the exception of T1r2, which was not detected in the mouse and human stomach or in the mouse colon. Using transgenic mice expressing enhanced green fluorescent protein under the control of the Trpm5 promoter, we found colocalization of Trpm5 and alpha-gustducin in tufted cells at the surface epithelium of the colon, but these cells did not express T1r3 or PLCbeta2. In the duodenal glands, 43%, 33%, and 38% of Trpm5-expressing cells also express PLCbeta2, T1r3, or alpha-gustducin, respectively. The duodenal gland cells that coexpress PLCbeta2 and Trpm5 morphologically resemble enteroendocrine cells. We found a large degree of colocalization of Trpm5, alpha-gustducin, T1r1, and T1r3 in tufted cells of the duodenal villi, but these cells rarely expressed PLCbeta2. The data suggest that these duodenal cells are possibly involved in sensing amino acids.

Isoleucine, an Essential Amino Acid, Induces the Expression of Human <i>β</i> Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

“…This is supported by the reduction of the effect of Ile on the induction of HBD2 when cells were treated with an inhibitor of the Gi subunit, Pertussis toxin. mGluR, GPR35 and the extracellular Ca the intracellular calcium ion concentration and activate the ERK signaling pathway, might therefore be candidates for sensing Ile [17][18][19]34]. Further analysis with knockout models for such GPCRs is needed to determine the specific GPCR responsible for the effects of Ile.…”

“…For example, glutamic acid is absorbed into the epithelia, and is also bound to a taste receptor which is one of the GPCRs. Many types of GPCRs, such as taste receptor and GPR35, are expressed in the intestinal epithelia [18][19][20]. In addi- tion, the functions of some GPCRs are associated with the expression of anti-microbial peptides in neutrophils and gingival cells [21,22].…”

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

“…It is proposed that nutrient sensing in the GI tract resembles taste signalling on the tongue (Rozengurt and Sternini, 2007;Sternini et al, 2008). Indeed, together with other taste signalling molecules, TRPM5 is expressed in epithelial cells of the gut (Bezencon et al, 2007;Jang et al, 2007;Young et al, 2009), and similar to their function in lingual taste cells, the GI taste signalling elements also respond to tastants in the gut lumen (Jang et al, 2007;Margolskee et al, 2007). TRPM5 is shown to be present in human duodenal L cells, where its expression is inversely related to the blood glucose concentration at least in subjects with type 2 diabetes (Jang et al, 2007;Young et al, 2009).…”

“…TRPM5 is shown to be present in human duodenal L cells, where its expression is inversely related to the blood glucose concentration at least in subjects with type 2 diabetes (Jang et al, 2007;Young et al, 2009). However, important species differences do exist as in the murine gut TRPM5 is not colocalized with any of the classical markers for EEC cells such as chromogranin A, 5-HT, glucagon-like peptide 1, ghrelin and cholecystokinin (Bezencon et al, 2007;Kokrashvili et al, 2009). In mouse, TRPM5 is mostly expressed in brush cells (Kaske et al, 2007;Bezencon et al, 2008), also referred to as tufted or caveolated cells (Sbarbati and Osculati, 2005a,b;Morroni et al, 2007).…”

Sweet taste signaling in the gut

“…A 1996 PNAS article by Höfer et al (7) showing that ␣-gustducin, the taste signaling protein first identified in Margolskee's laboratory (8), is localized in gut epithelial cells added considerable weight to this idea. More recently, several investigators reported the expression of bitter, sweet, and umami (savory) taste receptors in the gut (9)(10)(11). The next important step in this discovery process is to determine the function of these gut taste receptors in digestive and ingestive processing.…”