Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying.
Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)(3) receptors (5-HT(3)R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT(3)R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH(2)O). Pretreatment with the 5-HT(3)R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT(3)R, visualized with an antibody directed to the COOH terminus of the rat 5-HT(3)R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT(3)R and that the receptor mediates specific glucose-induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT(3)R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells.
Raybould
Helen E
HE
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California-Davis, 1321 Haring Hall, Davis, CA 95616, USA. heraybould@ucdavis.edu
Glatzle
Jorg
J
Robin
Carla
C
Meyer
James H
JH
Phan
Thomas
T
Wong
Helen
H
Sternini
Catia
C
D000818:Animals; D004386:Duodenum / Q000294:innervation / Q000378:metabolism / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D005746:Gastric Emptying / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007422:Intestines / Q000502:physiology; D008297:Male; D018613:Microscopy, Confocal; D009476:Neurons, Efferent / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D000077526:Tropisetron; D005947:Glucose