Effects of diet and the cholecystokinin antagonist; devazepide (L364,718) on CCK mRNA, and tissue and plasma CCK concentrations.
The mechanisms by which raw soya diets and CCK-receptor antagonists increase postprandial plasma CCK concentrations are not fully understood. Therefore we examined the effects of different diets including raw soya, 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 correlation between plasma and tissue CCK concentrations within each group (r = 0.94, P = 0.018) and between tissue CCK concentrations and CCK:beta-tubulin mRNA ratios (r = 0.91, P = 0.030). Animals fed ad libitum and treated with devazepide (1 mg kg-1) had higher CCK:beta-tubulin mRNA ratios, tissue CCK concentrations and plasma CCK concentrations than animals 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 intracellular changes devazepide did not elevate plasma CCK concentrations in the fasted state. Therefore, devazepide increases tissue concentrations of CCK but requires an additional dietary stimulus to raise plasma concentrations. These findings indicate that devazepide produces a dissociation between synthesis and release of CCK in fasted animals.
Playford
R J
RJ
Department of Medicine, RPMS, Hammersmith Hospital, London, UK.
King
A W
AW
Deprez
P H
PH
De-Belleroche
J
J
Freeman
T C
TC
Calam
J
J
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D015152:Blotting, Northern; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000097:blood; D020109:Devazepide; D005215:Fasting / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000096:biosynthesis
D001570:Benzodiazepinones; D012333:RNA, Messenger; D014404:Tubulin; D002766:Cholecystokinin; D020109:Devazepide