Regulation of cholecystokinin secretion by peptones and peptidomimetic antibiotics in STC-1 cells

被引:48
作者
Némoz-Gaillard, E
Bernard, C
Abello, J
Cordier-Bussat, M
Chayvialle, JA
Cuber, JC
机构
[1] Hop Edouard Herriot, INSERM, U45, Lyon, France
[2] INRA, Unite Ecol & Physiol Syst Digest, Jouy En Josas, France
关键词
D O I
10.1210/en.139.3.932
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Peptones are potent stimulants of cholecystokinin (CCK) release in rats, both in vivo and ex vivo in a model of isolated vascularly perfused duodeno;jejunum preparation and in vitro in the intestinal CCK-producing cell line STC-1. The underlying mechanisms were here investigated with this cell line. Protein hydrolysates from various origins (meat, casein, soybean, and ovalbumin; 0.5-1%, wt/vol) dose dependently increased CCK release. Cephalosporin antibiotics, which mimic tripeptides, also stimulated the release of CCK over the concentration range 1-20 mM. The study of concentration dependence of cephalosporin uptake indicated a passive diffusion process at either pH 7.4 or pH 6.0, thus arguing against the involvement of a peptide transporter in CCK secretion. After pertussis toxin treatment (200 ng/ml; 5 h), the peptone-and cephalexin-induced CCK secretion was significantly reduced, suggesting the involvement of pertussis toxin-sensitive heterotrimeric G protein(s) in the secretory activity of STC-1 cells. Consistent with this was the identification by Western blot of G(i2)alpha, G(i3)alpha, and G(o) alpha immunoreactivities in STC-1 cell extracts. Additionally, peptones and cephalexin increased the cellular content in inositol phosphates, whereas a mild increase in cAMP content was restricted to peptone-treated cells. Protein kinase A or C inhibition did not modify peptone-or antibiotic drug-evoked CCK release. The extracellular Ca2+ chelator EGTA(500 mu M) and the intracellular Ca2+ chelator BAPTA-AM [1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester; 20 mu M] abolished the peptone- and antibiotic drug-induced CCK release. Nifedipine and verapamil (10 mu M) reduced by about 50% the CCK secretion evoked by these two secretagogues. In conclusion, peptones and some cephalosporins are potent stimulants of CCK release in the STC-1 cell line. The cellular mechanisms involve pertussis toxin-sensitive G protein(s) and are dependent on Ca2+ availability. We suggest that the STC-1 cell line is a useful model to study the molecular basis of peptone-induced CCK secretion.
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页码:932 / 938
页数:7
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