TY - JOUR
T1 - Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons
AU - Babic, T.
AU - Troy, A. E.
AU - Fortna, S. R.
AU - Browning, K. N.
PY - 2012/10
Y1 - 2012/10
N2 - 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-HT3 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 (1.25-20mmolL-1) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular d-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current and the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5μmolL-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-HT3 receptor mediated responses. Conclusions & Inferences 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.
AB - 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-HT3 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 (1.25-20mmolL-1) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular d-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current and the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5μmolL-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-HT3 receptor mediated responses. Conclusions & Inferences 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.
UR - http://www.scopus.com/inward/record.url?scp=84866286932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866286932&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2982.2012.01987.x
DO - 10.1111/j.1365-2982.2012.01987.x
M3 - Article
C2 - 22845622
AN - SCOPUS:84866286932
SN - 1350-1925
VL - 24
SP - e476-e488
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 10
ER -