Trace amine associated receptor 1 (TAAR1) expression and modulation of inflammatory cytokine production in mouse bone marrow-derived macrophages: a novel mechanism for inflammation in ulcerative colitis

Actions of Trace Amines in the Brain-Gut-Microbiome Axis via Trace Amine-Associated Receptor-1 (TAAR1)

“…2b). The dynamic expression and localization of TAAR1 has been previously described (Bugda Gwilt et al 2019a;Sriram et al 2016;Stavrou et al 2018) and the production of trace amines by several species in the microbiome (e.g. Bargossi et al 2015;Pessione et al 2009;van Kessel et al 2019) may account for the predominant membranous localization of TAAR1 compared to colonic tissue.…”

“…Here, it is worth noting that despite no definitive function being identified in the polarized epithelium of the stomach and intestine, TAAR1 functionality has been described in the beta-cells of the pancreas, co-localized with PYY and GLP-1 in duodenal cells, and selective TAAR1 agonists resulted in elevated plasma levels of PYY and GLP-1 (Raab et al 2015), though these studies are not relevant to our discussion the brain-gutmicrobiome axis. Functional TAAR1 was found in almost all peripheral immune cells (Babusyte et al 2013;Panas et al 2012;Sriram et al 2016;Wasik et al 2012), with evidence that TAAR1 can modulate not only intracellular signaling (Panas et al 2012), but also immune cell functions such as chemotaxis (Babusyte et al 2013), phagocytosis [unpublished abstract, Miller Lab (Gwilt et al 2018] and altered expression of cytokines (Bugda Gwilt et al 2019a;Babusyte et al 2013). Immune cells are known to infiltrate the gastrointestinal tract with epithelial damage and inflammation, and given the reported chemotactic capacity of TAAR1 positive cells towards trace amines, TAAR1 positive immune cells should be noted in the gastrointestinal microenvironment given the propensity of patients with neuropsychiatric disorders to also present with peripheral inflammation.…”

“…Additionally, work from our lab has demonstrated that tyramine activation of bone marrow Fig. 2 Summary of TAAR1 expression in mouse gastrointestinal tissue Formalin fixed paraffin embedded mouse tissue (a, b) was stained with specific TAAR1 antibody, "D274" designed and published by the Miller lab (Bugda Gwilt et al 2019a). a TAAR1 localization is seen in apical epithelial cells and is both intracellularly and membrane localized in colon tissue.…”

“…b TAAR1 localization is seen primarily on membranes of the villus (fingerlike projections) and in the base of the crypts. c Ex vivo isolated enteric glial cultures were stained with TAAR1 (green) neurofilament medium (NEFM Red), Actin (pink) and DAPI (blue), demonstrating profound intracellular localization of TAAR1 in ex vivo enteric glial cultures 1 3 derived macrophages from C57BL/6 mice augments secretion of inflammatory cytokine gene expression, an effect that is attenuated by the specific TAAR1 antagonist EPPTB (Bugda Gwilt et al 2019a). Based on reports that dietary trace amines can activate human TAAR1 in primary epithelial cells (Ohta et al 2017), these specific effects of tyramine in in vitro human epithelial cell models may be attributed to a specific receptor-mediated mechanism by TAAR1 activation.…”

Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

“…Furthermore, we examined if Klamin ® induced relaxant effects via a direct action on the smooth muscle cells and/or via an indirect action involving neural pathways. Indeed, mouse and human studies reported that TAAR1 receptors are located in intestinal epithelial cells as well as enteric neurons of both submucosa and myenteric plexus [22,49,50].…”