The effects of treatment with CCK receptor antagonists or administration of an antisense oligonucleotide to the gastrin receptor, on gastrin-I and cholecystokinin-8-induced acid secretion in mouse stomach were evaluated. Administration of gastrin-I (1 μM) or chole-cystokinin-8 (30 nM) stimulated acid output at the rates of 2.6 ± 0.27 and 1.0 ± 0.21 μEqh-1, respectively. Gastrin-I-induced acid output was significantly blocked by pretreatment of stomachs with 3R[+]-N-[2,3-dihydro-1-methyl - 2 - oxo - 5 - phenyl - 1H - 1,4 - benzodiazepin-3-yl]-N [3-methlyphenyl]urea (L-365,260; 1 μM), but not by devazepide (L-364,718; 1 μM). Cholecystokinin-8-induced acid output, on the other hand, was sensitive to both L-365,260 (100 nM) and L-364,718 (100 nM). Administration of antisense, but not mismatch, oligonucleotide significantly reduced gastrin-induced acid output, while antisense oligonucleotide treatment had no effect on cholecystokinin-8-induced acid output. These results of antagonist and antisense oligonucleotide studies suggest that gastrin-I and cholecystokinin-8 may involve different receptor subtypes in stimulating gastric acid secretion in mice, and that antisense oligonucleotide administration may serve an useful tool in characterizing CCK/gastrin receptor subtypes.
- Gastric secretion
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