ATTENUATION OF GASTRIN-INDUCED GASTRIC-ACID SECRETION BY ANTISENSE OLIGONUCLEOTIDE TO THE CCKB GASTRIN RECEPTOR/

The effects of treatment with CCK receptor antagonists or administrati on 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 mu M) or cholecystokinin-8 ( 30 nM) stimulated acid output at the rates of 2.6 +/- 0.27 and 1.0 +/- 0.21 mu Eq h(-1), respectively. Gastrin-I-induced acid output was sig nificantly blocked by pretreatment of stomachs with methyl-2-oxo-5-phe nyl-1H-1,4-benzodiazepin-3-yl]-N [3-methlyphenyl]urea (L-365,260; 1 mu M), but not by devazepide (L-364,718; 1 mu M). Cholecystokinin-8-indu ced acid output, on the other hand, was sensitive to both L-365,260 (1 00 nM) and L-364,718 (100 nM). Administration of antisense, but not mi smatch, oligonucleotide significantly reduced gastrin-induced acid out put, while antisense oligonucleotide treatment had no effect on cholec ystokinin-8-induced acid output. These results of antagonist and antis ense oligonucleotide studies suggest that gastrin-I and cholecystokini n-8 may involve different receptor subtypes in stimulating gastric aci d secretion in mice, and that antisense oligonucleotide administration may serve an useful tool in characterizing CCK/gastrin receptor subty pes.