title: Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1.
abstract: Dietary protein is a major stimulant for cholecystokinin (CCK) secretion by the intestinal I cell, however, the mechanism by which protein is detected is unknown. Indirect functional evidence suggests that PepT1 may play a role in CCK-mediated changes in gastric motor function. However, it is unclear whether this oligopeptide transporter directly or indirectly activates the I cell. Using both the CCK-expressing enteroendocrine STC-1 cell and acutely isolated native I cells from CCK-enhanced green fluorescent protein (eGFP) mice, we aimed to determine whether PepT1 directly activates the enteroendocrine cell to elicit CCK secretion in response to oligopeptides. Both STC-1 cells and isolated CCK-eGFP cells expressed PepT1 transcripts. STC-1 cells were activated, as measured by ERK(1/2) phosphorylation, by both peptone and the PepT1 substrate Cefaclor; however, the PepT1 inhibitor 4-aminomethyl benzoic acid (AMBA) had no effect on STC-1 cell activity. The PepT1-transportable substrate glycyl-sarcosine dose-dependently decreased gastric motility in anesthetized rats but had no affect on activation of STC-1 cells or on CCK secretion by CCK-eGFP cells. CCK secretion was significantly increased in response to peptone but not to Cefaclor, cephalexin, or Phe-Ala in CCK-eGFP cells. Taken together, the data suggest that PepT1 does not directly mediate CCK secretion in response to PepT1 specific substrates. PepT1, instead, may have an indirect role in protein sensing in the intestine.
authors.affiliation: Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California-Davis, USA.
authors.forename: Alice P
authors.initials: AP
authors.lastname: Liou
authors.forename: Diana I
authors.initials: DI
authors.lastname: Chavez
authors.forename: Elvis
authors.initials: E
authors.lastname: Espero
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Hao
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wank
authors.forename: Helen E
authors.initials: HE
authors.lastname: Raybould
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002433:Cefaclor / Q000494:pharmacology; D002460:Cell Line; D002469:Cell Separation; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D000074011:Peptide Transporter 1; D010461:Peptones / Q000494:pharmacology; D010766:Phosphorylation; D011492:Protein Hydrolysates / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D014148:Tranexamic Acid / Q000378:metabolism
chemical_list: D000074011:Peptide Transporter 1; D010461:Peptones; D011492:Protein Hydrolysates; C489941:Slc15a1 protein, mouse; D027981:Symporters; D012313:RNA; D002433:Cefaclor; D014148:Tranexamic Acid; D002766:Cholecystokinin; D048049:Extracellular Signal-Regulated MAP Kinases