Reversal by omeprazole of the depression of gastrin cell function by fasting in the rat.
1. Gastrin (G)-cell function is controlled by gastric acid, which has inhibitory effects, and food in the gastric lumen, which has stimulatory effects. We have examined the role of acid in mediating the depression of G-cell function that occurs in fasting in the rat. 2. Rats were fasted for 48 h, and received either the H(+)-K(+)-ATPase inhibitor omeprazole, to reduce acid secretion, or vehicle. Basal acid secretion was not significantly different after fasting for 24 or 48 h. Fasted rats which received omeprazole were achlorhydric. 3. In rats treated with vehicle and fasted for 48 h, plasma and tissue gastrin concentrations were significantly depressed. The fall in both parameters suggests an inhibition of gastrin synthesis and consistent with this a decrease was observed in tissue gastrin mRNA abundance and in phosphorylation of progastrin-derived peptides. 4. In fasted rats treated with omeprazole, tissue gastrin concentrations were not significantly different from those of rats fed ad libitum, but plasma gastrin concentrations were significantly higher than in rats fed ad libitum. Gastrin mRNA abundance and the phosphorylation of progastrin-derived peptides in omeprazole-treated rats was not significantly different from rats fed ad libitum. 5. The data suggest that the depression of G-cell function which occurs in fasted rats can be attributed to the inhibitory action of intraluminal acid on the G-cell. Gastric acid appears to regulate several different aspects of G-cell function, including gastrin synthesis, post-translational processing and secretion.
Dimaline
R
R
Department of Physiology, University of Liverpool.
Evans
D
D
Varro
A
A
Dockray
G J
GJ
D000818:Animals; D005215:Fasting / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005755:Gastrins / Q000097:blood / Q000378:metabolism*; D009853:Omeprazole / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D005755:Gastrins; D012333:RNA, Messenger; D009853:Omeprazole