Activation of vagal afferents in the rat duodenum by protein digests requires PepT1.
Intestinal infusion of protein digests activates a vago-vagal reflex inhibition of gastric motility. Protein digests release cholecystokinin (CCK) from enteroendocrine cells; however, the precise cellular mechanisms leading to vagal afferent activation is unclear. The hypothesis that the oligopeptide transporter PepT1 plays a major role in the initiation of this vago-vagal reflex was tested by recording activation of duodenal vagal afferent activity and inhibition of gastric motility in response to protein hydrolysates in the presence of 4-aminomethylbenzoic acid (4-AMBA), a competitive inhibitor of PepT1, or 4-aminophenylacetic acid (4-APAA), an inactive 4-AMBA analog. Duodenal infusion of the protein hydrolysate increased vagal afferent discharge and inhibited gastric motility; these responses were abolished by concomitant infusion of 4-AMBA, but not 4-APAA. Duodenal infusion with Cefaclor, a substrate of PepT1, increased duodenal vagal afferent activity; Cefaclor and protein hydrolysates selectively activated CCK-responsive vagal afferents. This study demonstrates that products of protein digestion increase spontaneous activity of CCK-sensitive duodenal vagal afferents via a mechanism involving the oligopeptide transporter PepT1.
Darcel
N P
NP
Department of Anatomy, Physiology and Cell Biology, UC Davis School of Veterinary Medicine, Davis, CA 95616, USA.
Liou
A P
AP
Tomé
D
D
Raybould
H E
HE
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D004063:Digestion; D004386:Duodenum / Q000294:innervation*; D004594:Electrophysiology; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D000074011:Peptide Transporter 1; D010461:Peptones / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D062366:para-Aminobenzoates
D000074011:Peptide Transporter 1; D010461:Peptones; D011506:Proteins; C489940:Slc15a1 protein, rat; D027981:Symporters; D062366:para-Aminobenzoates; C015668:4-aminomethylbenzoic acid; D010129:4-Aminobenzoic Acid