Gastrin effects on isolated rat enterochromaffin-like cells following long-term hypergastrinaemia in vivo.
The enterochromaffin-like (ECL) cells play an important role in the regulation of gastric acid secretion. They respond to gastrin by a prompt increase in histamine secretion, an effect which is mediated by the CCK-(B)/gastrin receptor acting through the IP(3)/DAG pathway. In the rat, long-term treatment with acid secretion inhibitors induces hypergastrinaemia which, in turn, results in ECL cell hypertrophy and hyperplasia. The aim of the present study was to evaluate various functional parameters in acutely isolated rat ECL cells, following long-term hypergastrinaemia in vivo. Rats were treated with vehicle or a supramaximal daily dose of omeprazole for more than 10 weeks to ensure ECL cell hyperplasia. ECL cells were isolated from vehicle-treated animals and 24, 72 and 120 h after the last dose of omeprazole. The functional activity of the acutely isolated ECL cells was determined by measuring gastrin-and forskolin-induced histamine secretion. Changes in cytosolic free calcium upon gastrin stimulation were monitored by digital video imaging. ECL cells successively regained their ability to respond to gastrin following long-term hypergastrinaemia, reaching close to vehicle-treated levels 120 h after the last dose of omeprazole. In the rat, the response pattern of the ECL cells appears to normalise in parallel with the normalisation of plasma gastrin levels.
Andersson
N
N
AstraZeneca R and D Mölndal, S-431 83, Mölndal, Sweden.
Rhedin
M
M
Peteri-Brunbäck
B
B
Andersson
K
K
Cabero
J L
JL
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002452:Cell Count; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D019861:Enterochromaffin-like Cells / Q000187:drug effects*; D005260:Female; D005755:Gastrins / Q000097:blood / Q000494:pharmacology*; D006632:Histamine / Q000032:analysis; D006636:Histamine Release / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000897:Anti-Ulcer Agents; D005755:Gastrins; D006632:Histamine; D009853:Omeprazole; D002118:Calcium