Regulation of cholecystokinin secretion by bombesin in STC-1 cells

Abstract

Bombesin stimulates cholecystokinin (CCK) secretion, presumably by a direct effect on the intestinal CCK cell. The present objectives were to characterize bombesin-stimulated CCK release and to investigate the role of calcium in CCK secretion in an intestinal CCK-producing cell line (STC-1). Bombesin caused a dose-dependent release of CCK, which was reduced either in the absence of extracellular calcium or by calcium channel blockade, suggesting that influx of calcium is necessary for CCK secretion. Bombesin caused an increase in intracellular calcium concentration ([Ca2+]i) and increased efflux of 45Ca2+ from 45Ca(2+)-loaded cells. Radioligand binding studies and Northern analysis were consistent with the expression of a bombesin receptor. Thus bombesin stimulation of CCK release occurs via binding to a receptor and is dependent on increased [Ca2+]i. We propose that the STC-1 cell line may provide a useful model for studying the regulation of intestinal CCK secretion.

Duodenal Leptin Stimulates Cholecystokinin Secretion

“…Consistent with the results of previous studies (21,22), the neuropeptide bombesin (used as a positive control) stimulated the release of CCK in a concentration-dependent manner; 100 nmol/l stimulated an increase of 229.0 Ϯ 29.9% from the basal levels (P Ͻ 0.05 vs. basal) (Fig. 2A).…”

Signaling Mechanisms Underlying the Release of Glucagon-Like Peptide 1

“…In GLUTag cells loaded with fura2, 100 nmol/l bombesin triggered an increase in intracellular [Ca 2ϩ ] that was abolished by 10 mol/l thapsigargin ( Fig. 4A and B), suggesting that the Ca 2ϩ increment results from the release of Ca 2ϩ from intracellular stores, as has been reported previously in STC-1 cells (61,73). In secretion experiments, bombesin stimulated GLP-1 release approximately threefold in both the presence and absence of glucose (Fig.…”

Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

“…In recent years, STC-1 cells have emerged as a valuable model system for studying the regulation of GI peptide synthesis and release from intestinal endocrine cells. STC-1 cells synthesize and store CCK and release this hormonal peptide in response to bombesin (10,54,67), pituitary adenylate cyclase-activating polypeptide (7), leptin (22), fatty acids (8,66), orexin (36), aromatic amino acids (10), and peptidomimetic compounds (50,53). STC-1 cells have been also used as a model for studies of enteroendocrine cell differentiation (59), GI peptide processing (79,80) and regulation of CCK, glucose-dependent insulinotropic polypeptide, and proglucagon gene expression (2,20,31,37,58,78).…”

“…As a first step to examine these processes, we used the mouse enteroendocrine STC-1 cell line as a model system (61). These cells have been used for studying the regulation of GI hormone release in response to bombesin/gastrin-releasing peptide (10, 54, 67), pituitary adenylate cyclase-activating polypeptide (7), leptin (22), fatty acids (8,26,66), orexin (36), amino acids (10,38,41,43,67), and peptidomimetic compounds (50, 53). STC-1 cells produce and release cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide, secretin, and glucagon-like peptide-1 (GLP-1) (8,9,11,26,38) and have also served as a model for studies of enteroendocrine cell differentiation (59).…”