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The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin,(More)
Metabotropic glutamate receptors (mGluR) are classified into group I, II, and III mGluR. Group I (mGluR1, mGluR5) are excitatory, whereas group II and III are inhibitory. mGluR5 antagonism potently reduces triggering of transient lower esophageal sphincter relaxations and gastroesophageal reflux. Transient lower esophageal sphincter relaxations are mediated(More)
BACKGROUND AND AIMS Inhibitory G-protein-coupled receptors have demonstrated potential in treatment of gastroesophageal reflux disease (GERD) through actions on vagal afferent signaling. Metabotropic glutamate receptors (mGluR) belong to this receptor family and have great pharmacologic and molecular diversity, with 8 subtypes. We investigated mGluR in the(More)
Metabotropic glutamate receptors (mGluR) are classified into groups I (excitatory), II and III (inhibitory) mGluR. Activation of peripheral group III mGluR (mGluR4, mGluR6, mGluR7, mGluR8), particularly mGluR8, inhibits vagal afferent mechanosensitivity in vitro which translates into reduced triggering of transient lower oesophageal sphincter relaxations(More)
Vagal afferents that innervate gastric muscle or mucosa transmit distinct sensory information from their endings to the nucleus of the tractus solitarius (NTS). While these afferent subtypes are functionally distinct, no neurochemical correlate has been described and it is unknown whether they terminate in different central locations. This study aimed to(More)
Reducing colonic mechanosensitivity is an important potential strategy for reducing visceral pain. Mice lacking acid-sensing ion channels (ASIC) 1, 2, and 3 show altered colonic mechanosensory function, implicating ASICs in the mechanotransduction process. Deletion of ASICs affects mechanotransduction in visceral and cutaneous afferents differently,(More)
To investigate GABA(B) receptors along vagal afferent pathways, we recorded from vagal afferents, medullary neurons, and vagal efferents in ferrets. Baclofen (7-14 micromol/kg i.v.) reduced gastric tension receptor and nucleus tractus solitarii neuronal responses to gastric distension but not gastroduodenal mucosal receptor responses to cholecystokinin(More)
I ntestinal exposure to glucose stimulates the release of glucagon-like peptide-1 (GLP-1), slows subsequent gastric emptying, and reduces appetite. These responses are signaled, at least in part, by intestinal " sweet taste receptors " (STRs), including taste receptor type 1 members 2 and 3 (T1R2, T1R3), and their cellular signaling partners a-gustducin and(More)
GABA(B)-receptor (GABA(B)R) agonists reduce transient lower esophageal sphincter relaxation (TLESR) and reflux episodes through an action on vagal pathways. In this study, we determined whether GABA(B)R are expressed on vagal afferent neurones and whether they modulate distension-evoked discharge of vagal afferents in the isolated stomach. Vagal(More)
The detection of nutrients in the gastrointestinal (GI) tract is of fundamental significance to the control of motility, glycemia and energy intake, and yet we barely know the most fundamental aspects of this process. This is in stark contrast to the mechanisms underlying the detection of lingual taste, which have been increasingly well characterized in(More)