EFFECTS OF DIET AND THE CHOLECYSTOKININ ANTAGONIST - DEVAZEPIDE (L364,718) ON CCK MESSENGER-RNA, AND TISSUE AND PLASMA CCK CONCENTRATIONS

The mechanisms by which raw soya diets and CCK-receptor antagonists in crease postprandial plasma CCK concentrations are not fully understood . Therefore we examined the effects of different diets including raw s oya, and the effect of the potent CCK antagonist devazepide in the fed and fasted state on CCK concentrations in plasma and in the duodenal mucosa and on the duodenal CCK: beta-tubulin mRNA ratio in rats. Diets which stimulated high plasma CCK levels, such as raw soya, also gave the highest CCK tissue and mRNA concentrations with a close correlatio n between plasma and tissue CCK concentrations within each group (r = 0.94, P = 0.018) and between tissue CCK concentrations and CCK:beta-tu bulin mRNA ratios (r = 0.91, P = 0.030). Animals fed ad libitum and tr eated with devazepide (1 mg kg-1) had higher CCK:beta-tubulin mRNA rat ios, tissue CCK concentrations and plasma CCK concentrations than anim als injected with vehicle. Fasted animals treated with devazepide for 28 h also had higher CCK mRNA:beta-tubulin mRNA ratios (1.86 +/- 0.43 vs. 0.85 +/- 0.15, P < 0.05), and higher tissue CCK concentrations (0. 99 +/- 0.09 vs. 0.69 +/- 0.04, P < 0.01). However, despite these intra cellular changes devazepide did not elevate plasma CCK concentrations in the fasted state. Therefore, devazepide increases tissue concentrat ions of CCK but requires an additional dietary stimulus to raise plasm a concentrations. These findings indicate that devazepide produces a d issociation between synthesis and release of CCK in fasted animals.