title: Peptones stimulate cholecystokinin secretion and gene transcription in the intestinal cell line STC-1.
abstract: In rats, protein hydrolysates (peptones) stimulate cholecystokinin (CCK) release both in vivo and in a model of isolated vascularly perfused duodeno-jejunum. However, the mechanisms involved in peptone-induced stimulation of CCK cells are not well understood. In particular, the possibility that peptones may directly interact with CCK-producing cells to stimulate CCK release and gene transcription has not yet been examined. To test this hypothesis, we used the enteroendocrine cell line STC-1. Incubation of STC-1 cells for 2 h with albumin egg hydrolysate over the concentration range 0.01-1% (wt/ vol) caused a dose-dependent release of CCK, with a maximal increase at 1420% of the control value. In contrast, BSA (1%, wt/vol) or a mixture of amino acids (1%, wt/vol) induced a modest rise in CCK secretion. A dose-dependent, hydrolysate-specific, increase in the CCK steady state RNA level was also observed. It was detectable by 2-4 h of peptone treatment and sustained until 24-48 h. Peptones did not increase the CCK RNA level in the colonic CCK-producing cell line GLUTag or in nonintestinal CCK-expressing cell lines, namely the pancreatic cell line RINm5F and the medullar thyroid carcinoma cell line CA77. The peptone-induced increase in the CCK RNA level resulted from enhanced gene transcription, because labeled CCK transcripts from nuclear run-on incubations increased 3-fold when cells were incubated with peptones, whereas the level of beta-actin transcripts was not modified. Finally, peptones dose-dependently stimulated the transcriptional activity of an 800-bp fragment of CCK gene promoter transfected in STC-1 cells. These studies indicate that peptones specifically stimulate CCK secretion and gene transcription in the intestinal cell line STC-1, and that cis-acting elements conferring peptone inducibility are located in the first 800 bp of the 5'-flanking region of the CCK gene.
authors.affiliation: INSERM U-45, Hopital Edouard Herriot, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Cordier-Bussat
authors.forename: C
authors.initials: C
authors.lastname: Bernard
authors.forename: S
authors.initials: S
authors.lastname: Haouche
authors.forename: C
authors.initials: C
authors.lastname: Roche
authors.forename: J
authors.initials: J
authors.lastname: Abello
authors.forename: J A
authors.initials: JA
authors.lastname: Chayvialle
authors.forename: J C
authors.initials: JC
authors.lastname: Cuber
mesh_terms: D000818:Animals; D002460:Cell Line; D002766:Cholecystokinin / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D010461:Peptones / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D010461:Peptones; D012313:RNA; D002766:Cholecystokinin