M. Cordierbussat et al., PEPTONES STIMULATE CHOLECYSTOKININ SECRETION AND GENE-TRANSCRIPTION IN THE INTESTINAL-CELL LINE STC-1, Endocrinology, 138(3), 1997, pp. 1137-1144
In rats, protein hydrolysates (peptones) stimulate cholecystokinin (CC
K) 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 p
ossibility that peptones may directly interact with CCK-producing cell
s to stimulate CCK release and gene transcription has not yet been exa
mined. To test this hypothesis, me 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, hydrolysat
e-specific, increase in the CCK steady state RNA level was also observ
ed. It was detectable by 2-4 h of peptone treatment and sustained unti
l 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 thyroi
d carcinoma cell line CA77. The peptone-induced increase in the CCK RN
A level resulted from enhanced gene transcription, because labeled CCK
transcripts from nuclear run-on incubations increased S-fold when cel
ls were incubated with peptones, whereas the level of beta-actin trans
cripts was not modified. Finally, peptones dose-dependently stimulated
the transcriptional activity of an 800-bp fragment of CCK gene promot
er transfected in STC-1 cells. These studies indicate that peptones sp
ecifically stimulate CCK secretion and gene transcription in the intes
tinal cell line STC-1, and that cia-acting elements conferring peptone
inducibility are located in the first 800 bp of the 5'-flanking regio
n of the CCK gene.