Gastrin cell responses to acidification of the achlorhydric rat stomach.
In the rat, gastrin cells are normally exposed to the stimulatory effects of food and the inhibitory influences of acid in the gastric lumen. We have studied the effects of intragastric acid on gastrin cell function in animals in which the tonic inhibitory action of acid was removed by prior treatment with the proton pump blocker omeprazole. In fasted rats with gastric fistula treated with omeprazole, instillation of acid into the stomach produced a prompt decrease in plasma gastrin, but gastrin mRNA abundance showed a modest transient increase over a period of 2 h and thereafter no change; there was also a transient increase in tissue concentrations of the gastrin precursor progastrin that was compatible with increased gastrin synthesis. Concentrations of tissue gastrins, in general, increased after acid instillation, which can be attributed to continued synthesis in the presence of suppressed gastrin release. In rats fed ad libitum, a single dose of omeprazole (which produces achlorhydria for 24-30 h) produced an increase in plasma gastrin that peaked after 24 h and declined to control levels over the following 48 h; in contrast, gastrin mRNA abundance peaked 48 h after omeprazole before declining to control levels. The results indicate that whereas gastrin release might be promptly inhibited by intragastric acid, the changes in gastrin mRNA abundance are much slower: achlorhydria increases gastrin mRNA within 24 h, but acid takes longer to depress gastrin mRNA abundance. Over periods of a few hours, gastrin release and synthesis need not, therefore, change in parallel.
Dockray
G J
GJ
Physiological Laboratory, University of Liverpool, United Kingdom.
Dimaline
R
R
Forster
E R
ER
Evans
D
D
Sandvik
A
A
Varro
A
A
D000818:Animals; D005215:Fasting; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism*; D005755:Gastrins / Q000235:genetics / Q000378:metabolism*; D005766:Gastrointestinal Contents / Q000737:chemistry; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
D005755:Gastrins; D012333:RNA, Messenger; D009853:Omeprazole; D006851:Hydrochloric Acid