Involvement of Cholecystokinin (CCK) Receptor in the Regulation of Dexamethasone on Gastric Emptying in Male Rats

Abstract

Dexamethasone is a potent glucocorticoid, which has been used in the anti-inflammation therapy. It has been well known that the gastrointestinal (GI) motility is affected by stress. However, the role of glucocorticoids in regulating GI motility is unclear. The purpose of this study was to investigate the effect and action mechanism of dexamethasone on the GI motility. In the first study, the male rats were injected intraperitoneally (i.p.) with saline or dexamethasone (15 or 30 μg/ml/kg) 1 h before decapitation. In the second study, dexamethasone (30 μg/ml/kg) and lorglumide (a selective cholecystokinin A receptor, CCKA, antagonist) were injected intraperitoneally 60 min and 30 min prior to decapitation, respectively. All experimental animals were orally ingested with radioactive Na_2^(51)CrO_4 containing 10% charcoal by a PE-205 tubing into the stomach after a 24 h fast and then decapitated 15 min later. The small intestine was divided equally into ten segments. The radioactivity in stomach and each segment of intestine was counted by a gamma-counter. The ratios of gastric emptying and charcoal transit were calculated. Blood samples were collected. The concentrations of CCK and corticosterone in plasma samples were measured by radioimmunoassay, and those of serum adrenocorticotropin (ACTH) were measured by an enzyme immunoassay (EIA) kit. All data were expressed as mean ± s. e. mean, and analyzed by the analysis of variance (ANOVA). The differences between specific means were analyzed by Dunnett's test. The results demonstrate that dexamethasone dose dependently inhibited the level of serum ACTH and the gastric emptying, and the intestinal transit is also inhibited by dexamethasone at the dose of 15 μg/ml/kg. Plasma CCK and corticosterone concentrations were dose-dependently decreased by dexamethasone injection. Furthermore, after injection of lorglumide, the decreased gastric emptying caused by dexamethasone was restored to the control level. These results suggested that dexamethasone-induced inhibition of gastric emptying and intestinal transit is mediated by an action on CCKA receptor.