title: Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons.
abstract: BACKGROUND
  Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, and indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT(3) receptors.
  
  
  METHODS
  Whole-cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs' solution containing different concentrations of d-glucose (1.25-20 mmol L(-1)) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT(3) receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically.
  
  
  RESULTS
  Increasing or decreasing extracellular d-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current and the proportion of 5-HT(3) receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5 μmol L(-1)) suggesting involvement of a protein-trafficking pathway. Furthermore, l-glucose did not mimic the response of d-glucose implying that metabolic events downstream of neuronal glucose uptake are required to observe the modulation of 5-HT(3) receptor mediated responses.
  
  
  CONCLUSIONS
  These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged.
authors: Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
authors: T
authors: T
authors: Babic
authors: A E
authors: AE
authors: Troy
authors: S R
authors: SR
authors: Fortna
authors: K N
authors: KN
authors: Browning
mesh_terms: D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009475:Neurons, Afferent / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014630:Vagus Nerve / Q000378:metabolism*; D017833:Visceral Afferents / Q000378:metabolism
chemical_list: D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D005947:Glucose