People

The “Brain in the Gut” and Taste Receptors

My research program is concerned with the neuronal circuits that control gastrointestinal motility and the mechanisms that govern receptor-mediated responses in the enteric nervous system, the “brain in the gut”, and with chemosensing in the gastrointestinal tract. Currently, the main lines of my research include: (1) trafficking and signaling of G protein-coupled receptors induced by physiological and pathophysiological events with an emphasis on µ opioid receptor, the target of opioid analgesics used for pain control, which mediates opioid bowel syndrome and tolerance, and (2) role of taste signaling molecules in the regulation of gastrointestinal functions and feeding behavior. My group was the first to demonstrate that opioids differing in their ability to induce tolerance also differ in their efficiency to induce µOR trafficking, a process that regulates receptor signaling and function. The findings of ligand-selective and stimulation-dependent µOR internalization in enteric neurons are of importance for understanding the mechanisms underlying intracellular adaptations induced by prolonged activation of µORs, which hamper the use of opioids as analgesics. Furthermore, we have shown that µOR activation exerts a protective effect on acute intestinal inflammation through cytokine and NF-KB modulation. Another focus of my research is on the role of taste signaling molecules as chemosensory receptors in the gut mucosa, which are likely to modulate gut function and food intake through the release of signaling molecules by enteroendocrine cells, with emphasis on bitter taste receptors, a putative side of defense from potentially toxic substances, drugs and pathogens. The recent discovery that taste receptors for sweet and bitter are expressed throughout the body and not only in the tongue has given rise to the concept of a broader role for these receptors beyond “taste”. My lab has shown that taste signaling molecules are expressed by distinct populations of mucosal cells, including enteroendocrine cells, which synthesize peptides affecting motility, secretion, satiety and hunger, and that bitter taste receptors are regulated by feeding and different diets, suggesting they participate in the functional detection of intraluminal content and they serve as regulators of diet-induced responses by detecting changes in the microbiota.