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Glucose‐dependent trafficking of 5‐HT 3 receptors in rat gastrointestinal vagal afferent neurons
Author(s) -
Babic T.,
Troy A. E.,
Fortna S. R.,
Browning K. N.
Publication year - 2012
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2012.01987.x
Subject(s) - receptor , endocrinology , medicine , vagus nerve , 5 ht receptor , enteroendocrine cell , extracellular , enterochromaffin cell , biology , serotonin , chemistry , microbiology and biotechnology , stimulation , endocrine system , hormone
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. Key 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 μ mol 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 & 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.