Glycine-extended gastrin-17 stimulates acid secretion only via CCK-2 receptor-induced histamine release in the totally isolated vascularly perfused rat stomach.
The effects of gastrin precursors have been discussed during recent years. However, the mechanism for their action, whether through a novel receptor on the parietal cell or a cholecystokinin-2 (CCK-2) receptor on the enterochromaffin like (ECL) cells, is still not settled. This study examines the effect of glycine-extended gastrin-17 (Gly-G-17), the main non-amidated gastrin precursor, on gastric acid secretion and histamine release in the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at the concentrations from 0.52 to 520 nmol L(-1) was administered to the totally isolated vascularly perfused rat stomach. Glycine-extended gastrin-17 at 52 or 520 nmol L(-1), and gastrin-17 at 0.52 nmol L(-1)were co-administered to examine whether glycine-extended gastrin augmented maximal gastrin stimulated acid secretion and histamine release. Both Gly-G-17 at 52 nmol L(-1) and gastrin-17 (G-17) at 0.52 nmol L(-1) were administered together with the histamine-2 receptor antagonist ranitidine at 10 micromol L(-1). Gastric acid and venous histamine output were measured. Glycine-extended gastrin-17 at lower concentrations from 0.52 to 5.2 nmol L(-1) did not stimulate gastric acid output or histamine release, whereas higher concentrations from 52 to 520 nmol L(-1) elicited a concentration-dependent increase in acid secretion and histamine release. The outputs of acid and histamine at 520 nmol L(-1) Gly-G-17 were at the same level as those found for G-17 at its maximally effective concentration of 0.52 nmol L(-1). Glycine-extended gastrin-17 at maximally effective concentration of 520 nmol L(-1) did not augment maximal gastrin stimulated acid secretion or histamine release. Ranitidine inhibited G-17 and Gly-G-17 stimulated acid secretion to a similar degree. This study confirms that the stimulatory effect of Gly-G-17 on gastric acid secretion is via a CCK-2 receptor on the ECL cell.
Cui
G-L
GL
Department of Intra-abdominal Diseases, Faculty of Medicine, Norwegian University of Science and Technology, N-7006 Trondheim, Norway.
Sandvik
A K
AK
Munkvold
B
B
Waldum
H L
HL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013270:Stomach / Q000166:cytology / Q000187:drug effects*
D004338:Drug Combinations; D005755:Gastrins; D011949:Receptors, Cholecystokinin; C086854:glycine-extended gastrin 17; C013550:gastrin 17; D006632:Histamine; D011899:Ranitidine