Luminal CCK-releasing factor stimulates CCK release from human intestinal endocrine and STC-1 cells

Abstract

CCK is secreted into the blood from intestinal endocrine cells following ingestion of a meal. Recently, it has been demonstrated that the ability of certain foods to stimulate CCK release is mediated by endogenously produced CCK-releasing factors. A newly discovered luminal CCK-releasing factor (LCRF) is secreted into the intestine, where it stimulates CCK secretion. However, the mechanism whereby LCRF affects intestinal epithelial cells is unknown. The current study was designed to determine whether LCRF has a direct effect on CCK cells to stimulate hormone secretion. In dispersed human intestinal mucosal cells, LCRF (5-200 nM) significantly stimulated CCK release in a concentration-dependent manner. This stimulatory effect was absent in calcium-free media and was inhibited by the L-type calcium-channel blockers diltiazem and nifedipine. To examine direct cellular effects of LCRF on CCK cells, further studies were conducted in the CCK-containing enteroendocrine cell line STC-1. As in native cells, LCRF significantly stimulated CCK release from STC-1 cells in a calcium-dependent manner. In cells loaded with a calcium-sensitive dye, LCRF stimulation produced a rapid increase in intracellular calcium. To examine the electrophysiological basis for this stimulation, whole cell recordings were made from STC-1 cells. Whole cell calcium currents were identified under basal conditions; moreover, calcium-channel activity was increased by LCRF. These studies demonstrate that 1) LCRF has a direct effect on human intestinal cells to stimulate CCK secretion, 2) stimulated hormone release is calcium dependent, and 3) LCRF activates calcium currents in CCK cells, which leads to CCK secretion.

Soybean β-Conglycinin Bromelain Hydrolysate Stimulates Cholecystokinin Secretion by Enteroendocrine STC-1 Cells to Suppress the Appetite of Rats under Meal-Feeding Conditions

“…8) However, we and other researchers have found that dietary protein/peptide acted directly on CCK-producing EECs to stimulate CCK release and suppress appetite independently from endogenous CCK-releasing peptides. [9][10][11][12][13] These findings were further supported by the result that peptones stimulated CCK secretion in CCK-producing murine enteroendocrine STC-1 cell line. [14][15][16][17][18] We have previously demonstrated that an intraduodenal infusion of peptides from a peptic hydrolysate (peptone) of soybean -conglycinin suppressed the food intake by duodenally-cannulated rats and directly stimulated CCK release from the EECs.…”

Pork Peptone Stimulates Cholecystokinin Secretion from Enteroendocrine Cells and Suppresses Appetite in Rats

“…Conversely, it has been shown that endogenous CCK-releasing peptides also stimulate CCK release from STC-1 cells. 18) Therefore, despite speculation on a direct interaction of the peptide with CCKproducing cells, we argue another possibility: that peptone also interacts with endogenous CCK-releasing peptide-producing cells to release CCK. In our binding studies, we used whole BBM of rat small intestinal mucosal cells consisting of several kinds of cells, including I-cells.…”

“…16) An enteroendocrine cell line, STC-1 cells have been shown to be a suitable model for studying CCK release, which responds to several physiological stimulants including nutrients, hormones, and luminal CCKreleasing factors. 11,12,17,18) The purpose of the present study was to find new appetite suppressing peptides from dietary protein sources, other than -conglycinin, that involve with CCK release. The effects of dietary proteins derived from animal sources on CCK release have not yet been studied extensively by in vitro or in vivo models.…”

TRPA1 channel activation induces cholecystokinin release via extracellular calcium

“…The L-type voltage-gated calcium channel blockers nimodipine and nifedipine have been previously shown to totally block the L-type voltage-gated channels activated by various stimuli in STC-1 cells in the same or even lower concentrations that used in this study [18,19,23,24]. Blocking the L-type voltage-gated calcium channels only partially (by 36%) reduced the AITC induced CCK release suggesting that voltage-gated calcium channels contribute to some extent to the calcium influx in response to AITC stimulation, yet the major proportion of the increased calcium levels is due to calcium influx via TRPA1.…”