Catia Sternini, Ph.D.

Research

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 changing in the microbiota. Biography 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.

Publications

Anselmi Laura, Huynh Jennifer, Vegezzi Gaia, Sternini Catia Effects of methylnaltrexone on guinea pig gastrointestinal motility. Naunyn-Schmiedeberg’s archives of pharmacology. 2013; 386(4): 279-86.

Latorre Rocco, Mazzoni Maurizio, De Giorgio Roberto, Vallorani Claudia, Bonaldo Alessio, Gatta Pier Paolo, Corinaldesi Roberto, Ruggeri Eugenio, Bernardini Chiara, Chiocchetti Roberto, Sternini Catia, Clavenzani Paolo Enteroendocrine profile of alpha-transducin immunoreactive cells in the gastrointestinal tract of the European sea bass (Dicentrarchus labrax). Fish physiology and biochemistry. 2013; 145(3): .

Mazzoni Maurizio, De Giorgio Roberto, Latorre Rocco, Vallorani Claudia, Bosi Paolo, Trevisi Paolo, Barbara Giovanni, Stanghellini Vincenzo, Corinaldesi Roberto, Forni Monica, Faussone-Pellegrini Maria S, Sternini Catia, Clavenzani Paolo Expression and regulation of alpha-transducin in the pig gastrointestinal tract. Journal of cellular and molecular medicine. 2013; 17(4): 466-74.

Sternini Catia In search of a role for carbonation: is this a good or bad taste?. Gastroenterology. 2013; 145(3): 500-3. Anselmi Laura, Jaramillo Ingrid, Palacios Michelle, Huynh Jennifer, Sternini Catia Ligand-induced mu opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl. Journal of neuroscience research. 2013; 91(6): 854-60.

Saccani Francesca, Anselmi Laura, Jaramillo Ingrid, Bertoni Simona, Barocelli Elisabetta, Sternini Catia Protective role of mu opioid receptor activation in intestinal inflammation induced by mesenteric ischemia/reperfusion in mice. Journal of neuroscience research. 2012; 90(11): 2146-53.

Patierno Simona, Anselmi Laura, Jaramillo Ingrid, Scott David, Garcia Rachel, Sternini Catia Morphine induces mu opioid receptor endocytosis in guinea pig enteric neurons following prolonged receptor activation. Gastroenterology. 2011; 140(2): 618-26.

Young Steven H, Rey Osvaldo, Sternini Catia, Rozengurt Enrique Amino acid sensing by enteroendocrine STC-1 cells: role of the Na+-coupled neutral amino acid transporter 2. American journal of physiology. Cell physiology. 2010; 298(6): C1401-13.

Hao Shuzhen, Dulake Michelle, Espero Elvis, Sternini Catia, Raybould Helen E, Rinaman Linda Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands. American journal of physiology. Regulatory, integrative and comparative physiology. 2009; 296(3): R528-36.

Anselmi Laura, Stella Salvatore L, Brecha Nicholas C, Sternini Catia Galanin inhibition of voltage-dependent Ca(2+) influx in rat cultured myenteric neurons is mediated by galanin receptor 1. Journal of neuroscience research. 2009; 87(5): 1107-14.

Sternini Catia, Anselmi Laura, Rozengurt Enrique Enteroendocrine cells: a site of ‘taste’ in gastrointestinal chemosensing. Current opinion in endocrinology, diabetes, and obesity. 2008; 15(1): 73-8.

Hao Shuzhen, Sternini Catia, Raybould Helen E Role of CCK1 and Y2 receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands. American journal of physiology. Regulatory, integrative and comparative physiology. 2008; 294(1): R33-8.

Kimura T, Koya RC, Anselmi L, Sternini C, Wang HJ, Comin-Anduix B, Prins RM, Faure-Kumar E, Rozengurt N, Cui Y, Kasahara N, Stripecke R. Lentiviral Vectors with CMV or MHCII Promoters Administered In Vivo: Immune Reactivity Versus Persistence of Expression. Mol Ther 2007; 15(7): 1390-9.

Dellabianca A, Sacchi M, Anselmi L, De Amici E, Cervio E, Agazzi A, Tonini S, Sternini C, Tonini M, Candura SM. Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea. Br J Pharmacol 2007; 150(2): 220-6.

Rozengurt Enrique, Sternini Catia Taste receptor signaling in the mammalian gut. Current opinion in pharmacology. 2007; 7(6): 557-62. Sternini C. Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing. Am J Physiol Gastrointest LIver Physiol 2007; 292(2): G457-61.

Sternini Catia Taste receptors in the gastrointestinal tract. IV. Functional implications of bitter taste receptors in gastrointestinal chemosensing. American journal of physiology. Gastrointestinal and liver physiology. 2007; 292(2): G457-61.

Rozengurt N, Wu SV, Chen MC, Huang C, Sternini C, Rozengurt E. Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. Am J Physiol Gastrointest Liver Physiol 2006; 291(5): G792-802.

Rozengurt Nora, Wu S Vincent, Chen Monica C, Huang Carlos, Sternini Catia, Rozengurt Enrique Colocalization of the alpha-subunit of gustducin with PYY and GLP-1 in L cells of human colon. American journal of physiology. Gastrointestinal and liver physiology. 2006; 291(5): G792-802.

Freeman SL, Glatzle J, Robin CS, Valdellon M, Sternini C, Sharp JW, Raybould HE. Ligand-induced 5-HT3 receptor internalization in enteric neurons in rat ileum. Gastroenterology 2006; 131(1): 97-107.

Freeman Samara L, Glatzle Jorg, Robin Carla S, Valdellon Melissa, Sternini Catia, Sharp James W, Raybould Helen E Ligand-induced 5-HT3 receptor internalization in enteric neurons in rat ileum. Gastroenterology. 2006; 131(1): 97-107.

Cattaruzzza F, Cenac N, Barocelli E, Impicciatore M, Hyun E, Vergnolle N, Sternini C. Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents. Am J Pathol 2006; 169(1): 177-88.

Cattaruzza Fiore, Cenac Nicolas, Barocelli Elisabetta, Impicciatore Mariannina, Hyun Eric, Vergnolle Nathalie, Sternini Catia Protective effect of proteinase-activated receptor 2 activation on motility impairment and tissue damage induced by intestinal ischemia/reperfusion in rodents. The American journal of pathology. 2006; 169(1): 177-88.

Bradesi Sylvie, Kokkotou Efi, Simeonidis Simos, Patierno Simona, Ennes Helena S, Mittal Yash, McRoberts James A, Ohning Gordon, McLean Peter, Marvizon Juan Carlos, Sternini Catia, Pothoulakis Charalabos, Mayer Emeran A The role of neurokinin 1 receptors in the maintenance of visceral hyperalgesia induced by repeated stress in rats. Gastroenterology. 2006; 130(6): 1729-42.

Tonini M, Vicini R, Cervio E, De Ponti F, De Giorgio R, Barbara G, Stanghellini V, Dellabianca A, Sternini C. 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum. Gastroenterology 2005; 129(5): 1557-66.

Tonini Marcello, Vicini Riccardo, Cervio Elisabetta, De Ponti Fabrizio, De Giorgio Roberto, Barbara Giovanni, Stanghellini Vincenzo, Dellabianca Antonio, Sternini Catia 5-HT7 receptors modulate peristalsis and accommodation in the guinea pig ileum. Gastroenterology. 2005; 129(5): 1557-66.

Calcina F, Barocelli E, Bertoni S, Furukawa O, Kaunitz J, Impicciatore M, Sternini C. Effect of N-methyl-d-aspartate receptor blockade on neuronal plasticity and gastrointestinal transit delay induced by ischemia/reperfusion in rats. Neuroscience 2005; 134(1): 39-49.

Anselmi L, Lakhter A, Hirano AA, Tonini M, Sternini C. Expression of galanin receptor messenger RNAs in different regions of the rat gastrointestinal tract. Peptides 2005; 26(5): 815-9.

Anselmi Laura, Lakhter Alexander, Hirano Arlene A, Tonini Marcello, Sternini Catia Expression of galanin receptor messenger RNAs in different regions of the rat gastrointestinal tract. Peptides. 2005; 26(5): 815-9.

Anselmi L, Stella SL Jr, Lakhter A, Hirano A, Tonini M, Sternini C. Galanin receptors in the rat gastrointestinal tract. Neuropeptides 2005; 39(3): 349-52.

Anselmi Laura, Stella Salvatore L, Lakhter Alexander, Hirano Arlene, Tonini Marcello, Sternini Catia Galanin receptors in the rat gastrointestinal tract. Neuropeptides. 2005; 39(3): 349-52.

Anselmi L, Cervio E, Guerrini S, Vicini R, Agazzi A, Dellabianca A, Reeve JR jr, Tonini M, Sternini C. Identification of galanin receptor 1 on excitatory motor neurons in the guinea pig ileum. Neurogastroenterol Motil 2005; 17(2): 273-80.

Cottrell GS, Roosterman D, Marvizon JC, Song B, Wick E, Pikios S, Wong H, Berthelier C, Tang Y, Sternini C, Bunnett NW, Grady EF. Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. J Comp Neurol 2005; 490(3): 239-55.

Cottrell Graeme S, Roosterman Dirk, Marvizon Juan-Carlos, Song B, Wick Elizabeth, Pikios Stella, Wong Helen, Berthelier Claire, Tang Yat, Sternini Catia, Bunnett Nigel W, Grady Eileen F Localization of calcitonin receptor-like receptor and receptor activity modifying protein 1 in enteric neurons, dorsal root ganglia, and the spinal cord of the rat. The Journal of comparative neurology. 2005; 490(3): 239-55.

Patierno S, Zellalem W, Ho A, Parsons CG, Lloyd KC, Tonini M, Sternini C. N-methyl-D-aspartate receptors mediate endogenous opioid release in enteric neurons after abdominal surgery. Gastroenterology 2005; 128(7): 2009-19.

Patierno Simona, Zellalem Wubanche, Ho Anthony, Parsons Chris G, Lloyd K C Kent, Tonini Marcello, Sternini Catia N-methyl-D-aspartate receptors mediate endogenous opioid release in enteric neurons after abdominal surgery. Gastroenterology. 2005; 128(7): 2009-19.

Lu YC, Sternini C, Rozengurt E, Zhukova E. Release of transgenic human insulin from gastric g cells: a novel approach for the amelioration of diabetes. Endocrinology 2005; 146(6): 2610-9.

Lu Yu-Chun, Sternini Catia, Rozengurt Enrique, Zhukova Elena Release of transgenic human insulin from gastric g cells: a novel approach for the amelioration of diabetes. Endocrinology. 2005; 146(6): 2610-9.

Patierno, S Raybould, HE Sternini, C Abdominal surgery induces mu opioid receptor endocytosis in enteric neurons of the guinea-pig ileum. Neuroscience. . 2004; 123(1): 101-9.

Guerrini S, Raybould HE, Anselmi L, Agazzi A, Cervio E, Reeve JR Jr, Tonini M, Sternini C. Role of galanin receptor 1 in gastric motility in rat. Neurogastroenterol Motil 2004; 16(4): 429-38.

Sternini C, Anselmi L, Guerrini S, Cervio E, Pham T, Balestra B, Vicini R, Baiardi P, D’agostino GL, Tonini M. Role of galanin receptor 1 in peristaltic activity in the guinea pig ileum. Neuroscience 2004; 125(1): 103-12.

Sternini C, Patierno S, Selmer IS, Kirchgessner A. The opioid system in the gastrointestinal tract. Neurogastroenterol Motil 2004; 16(Suppl 2): 3-16.

Raybould Helen E, Glatzle Jorg, Robin Carla, Meyer James H, Phan Thomas, Wong Helen, Sternini Catia Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying. American journal of physiology. Gastrointestinal and liver physiology. 2003; 284(3): G367-72.

Raybould, HE Glatzle, J Robin, C Meyer, JH Phan, T Wong, H Sternini, C Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying. American journal of physiology. Gastrointestinal and liver physiology. 2003; 284(3): G367-72.

Minnis, JG Patierno, S Kohlmeier, SE Brecha, NC Tonini, M Sternini, C Ligand-induced mu opioid receptor endocytosis and recycling in enteric neurons. Neuroscience. . 2003; 119(1): 33-42.

Ho, A Lievore, A Patierno, S Kohlmeier, SE Tonini, M Sternini, C Neurochemically distinct classes of myenteric neurons express the mu-opioid receptor in the guinea pig ileum. The Journal of comparative neurology. . 2003; 458(4): 404-11.

Ho Anthony, Lievore Annarita, Patierno Simona, Kohlmeier Sean E, Tonini Marcello, Sternini Catia Neurochemically distinct classes of myenteric neurons express the mu-opioid receptor in the guinea pig ileum. The Journal of comparative neurology. 2003; 458(4): 404-11.

Pham, T Guerrini, S Wong, H Reeve, J Sternini, C Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small intestine. The Journal of comparative neurology. . 2002; 450(3): 292-302.

Pham Thomas, Guerrini Stefania, Wong Helen, Reeve Joseph, Sternini Catia Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small intestine. The Journal of comparative neurology. 2002; 450(3): 292-302.

Glatzle, J Sternini, C Robin, C Zittel, TT Wong, H Reeve, JR Raybould, HE Expression of 5-HT3 receptors in the rat gastrointestinal tract. Gastroenterology. . 2002; 123(1): 217-26.

Glatzle Jörg, Sternini Catia, Robin Carla, Zittel Tilman T, Wong Helen, Reeve Joseph R, Raybould Helen E Expression of 5-HT3 receptors in the rat gastrointestinal tract. Gastroenterology. 2002; 123(1): 217-26.

Salvioli Beatrice, Bovara Monica, Barbara Giovanni, De Ponti Fabrizio, Stanghellini Vincenzo, Tonini Marcello, Guerrini Stefania, Cremon Cesare, Degli Esposti Marzia, Koumandou Magdalina, Corinaldesi Roberto, Sternini Catia, De Giorgio Roberto Neurology and neuropathology of the pancreatic innervation. JOP : Journal of the pancreas. 2002; 3(2): 26-33.

Schmidlin, F Dery, O DeFea, KO Slice, L Patierno, S Sternini, C Grady, EF Bunnett, NW Dynamin and Rab5a-dependent trafficking and signaling of the neurokinin 1 receptor. The Journal of biological chemistry. . 2001; 276(27): 25427-37.

Zhukova, E Afshar, A Ko, J Popper, P Pham, T Sternini, C Walsh, JH Expression of the human insulin gene in the gastric G cells of transgenic mice. Transgenic research. . 2001; 10(4): 329-41.

Wong, HC Sternini, C Yang, H Pham, T Walsh, JH Monoclonal antibody to rat galanin: production, characterization, and in vivo immunoneutralization activity. Hybridoma. . 2001; 20(2): 109-15.

Tonini, M Spelta, V De Ponti, F De Giorgio, R D’Agostino, G Stanghellini, V Corinaldesi, R Sternini, C Crema, F Tachykinin-dependent and -independent components of peristalsis in the guinea pig isolated distal colon. Gastroenterology. . 2001; 120(4): 938-45.

Melone, M Brecha, NC Sternini, C Evans, C Conti, F Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex. Neuroscience. . 2000; 100(3): 439-43.

De Giorgio R, Arakawa J, Wetmore CJ, Sternini C Neutrophin-3 and neutrophin receptor immunoreactivity in peptidergic enteric neurons. Peptides 2000; 21: 1421-26.

Sternini, C Brecha, NC Minnis, J D’Agostino, G Balestra, B Fiori, E Tonini, M Role of agonist-dependent receptor internalization in the regulation of mu opioid receptors. Neuroscience. . 2000; 98(2): 233-41.

Tonini, M De Giorgio, R De Ponti, F Sternini, C Spelta, V Dionigi, P Barbara, G Stanghellini, V Corinaldesi, R Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations. British journal of pharmacology. . 2000; 129(1): 12-20.

McConalogue, K Grady, EF Minnis, J Balestra, B Tonini, M Brecha, NC Bunnett, NW Sternini, C Activation and internalization of the mu-opioid receptor by the newly discovered endogenous agonists, endomorphin-1 and endomorphin-2. Neuroscience. . 1999; 90(3): 1051-9.

Sternini C, Wong H, Pham T, De Giorgio R, Miller LJ, Kuntz SM, Reeve JR, Walsh JH, Raybould HE Expression of cholecystokinin A receptors in neurons innvervating the rat stomach and intestine. Gastroenterology 1999; 117: 1136-46.

Lecci A, De Giorgio R, Bartho L, Sternini C, Tramontana M, Corinaldesi R, Giuliani S, Maggi CA Tachykinin NK(1)receptor-mediated inhibitory responses in the guinea pig small intestine. Neuropeptides 1999; 33: 91-97.

Sternini C, Wong H, Wu SV, De Giorgio R, Yang M, Reeve J, Jr., Brecha NC, Walsh JH Somatostatin 2A receptor is expressed by enteric neruons, and by interstitial cells of Cajal and enterochromaffin-like cells. Journal of Comparative Neurology 1997; 386: 396-408.

Sternini, C Spann, M Anton, B Keith, DE Bunnett, NW von Zastrow, M Evans, C Brecha, NC Agonist-selective endocytosis of mu opioid receptor by neurons in vivo. Proceedings of the National Academy of Sciences of the United States of America. . 1996; 93(17): 9241-6.

Sternini, C Su, D Gamp, PD Bunnett, NW Cellular sites of expression of the neurokinin-1 receptor in the rat gastrointestinal tract. The Journal of comparative neurology. . 1995; 358(4): 531-40.

Duraffourd Celine, Kumala Erica, Anselmi Laura, Brecha Nicholas C, Sternini Catia Opioid-induced mitogen-activated protein kinase signaling in rat enteric neurons following chronic morphine treatment. PloS one. 2014; 9(10): e110230.

Vegezzi Gaia, Anselmi Laura, Huynh Jennifer, Barocelli Elisabetta, Rozengurt Enrique, Raybould Helen, Sternini Catia Diet-induced regulation of bitter taste receptor subtypes in the mouse gastrointestinal tract. PloS one. 2014; 9(9): e107732.

Anselmi L, Huynh J, Duraffourd C, Jaramillo I, Vegezzi G, Saccani F, Boschetti E, Brecha N C, De Giorgio R, Sternini C Activation of mu opioid receptors modulates inflammation in acute experimental colitis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 2015; 27(4): 509-23.