Regulation of intestinal cholecystokinin and somatostatin mRNA by bombesin in rats

Abstract

The neuropeptide bombesin has been shown to stimulate secretion of several gastrointestinal hormones, including cholecystokinin (CCK). We have previously demonstrated that stimulation of CCK release by feeding is associated with an increase in steady-state intestinal CCK mRNA levels. The purpose of the present study was to determine whether bombesin stimulates CCK release in rats and, if so, to determine whether bombesin regulates CCK mRNA levels in a manner similar to that of feeding. To establish a proper dose of bombesin for stimulating CCK release, rats received 1-h intravenous infusions of 0.25, 1, 4, or 16 micrograms.kg-1.h-1 bombesin. Basal plasma CCK levels averaged 1.8 +/- 0.4 pM and increased to peak levels of 2.9 +/- 0.6 pM within 15 min of infusion with 4 micrograms.kg-1.h-1 bombesin (the maximally effective dose). With the use of this dose, rats then received infusions of bombesin or saline lasting up to 24 h. At 1, 2, 4, and 24 h, animals were killed for collection of plasma for CCK measurements and of intestine for measurements of intestinal CCK and somatostatin mRNA levels. Bombesin treatment stimulated an increase in plasma CCK levels at 1 h, but levels declined to basal by 4 h, where they remained at 24 h. Despite increasing plasma CCK levels, bombesin infusion, unlike dietary stimulation, had no effect on duodenal CCK mRNA levels. Finally, to determine whether the decrease in plasma CCK levels after prolonged bombesin treatment was due to tachyphylaxis, rats treated with bombesin for 4 h were also fed soybean trypsin inhibitor (a known stimulus of CCK secretion).(ABSTRACT TRUNCATED AT 250 WORDS)

Dynamics of appetite-mediated gene expression in daidzein-fed female rats in the meal-feeding method

“…There is the possibility that daidzein feeding may enhance eating relative expression of CCK mRNA through change in the expression of other genes. Although CCK gene expression is not necessarily linked to secretion, 42) suppressive effect on food intake of CCK is associated with the amount of secreted it. Analyses of protein levels will be needed to determine whether the anorectic effect of daidzein is partially mediated by increases in CCK expression.…”

Deficits in gastrointestinal responses controlling food intake and body weight

“…BBS inhibits food intake independently of CCK as evidenced by the finding that BBS, but not CCK, reduces food intake following vagotomy (200,201). Although BBS appears to utilize a nonvagal pathway unlike CCK, BBS stimulates CCK secretion (51,105), and the CCK-1R antagonist, proglumide, partially blocks the effect of high doses of BBS on food intake (42). In addition to being less sensitive to CCK, rats maintained on an Fig.…”

Regulation of cholecystokinin secretion in humans

“…Gastrin-releasing peptide (GRP) stimulates CCK release and CCK-secreting cells possess GRP receptors. 44,45 Thus, GRP-containing nerves may modulate CCK release. The effect of vagal innervation on CCK secretion has been examined in vagotomized patients, who demonstrated an exaggerated CCK response to a liquid meal.…”