Activation of Vagal Afferents in the Rat Duodenum by Protein Digests Requires PepT11,2

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ABSTRACT

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.

Key Words

nutrient detection
protein
vagal afferents
PepT1
cholecystokinin

Abbreviations

4-AMBA
4-aminomethylbenzoic acid
4-APAA
aminophenylacetic acid
CCK
cholecystokinin
CCK1R
cholecystokinin 1 receptor
ERK
extracellular signal-regulated kinase
GLP
glucagon-like peptide
i.a.
intra-arterial
i.d.
intraduodenal
IGP
intragastric pressure
MAP
mitogen-activated protein kinase
RQ
response quotient

Cited by (0)

1

Presented in part at Experimental Biology 04, April 17–21, 2004, Washington, DC [Liou, A., Darcel, N., Tomé, D. & Raybould, H. E. (2004) Vagally-mediated inhibition of gastric motility in response to protein digest is dependent on the oligopeptide transporter PepT1. FASEB J. 18: A230 (abs.)] and [Darcel, N., Liou, A., Tomé, D. & Raybould, H. E. (2004) Proton-coupled oligopeptide transporter PepT1 is required for duodenal vagal afferent activation by protein digest. FASEB J. 18: A456 (abs.)].

2

Supported by National Institutes of Health RO1DK 41004 (H.E.R.) and by Achievement Rewards for College Scientists Foundation scholarship (A.L.).