Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

Authors


Address for Correspondence
Dr. Kirsteen N. Browning, Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, MC H109, Hershey, PA 17033, USA.
Tel: 717 531 8267; fax: 717 531 5184;
e-mail: knb13@psu.edu

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-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 (1.25–20 mmol L−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 (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-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.

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