Inhibition of gastrin‐ and histamine‐stimulated gastric acid secretion by gastrin and cholecystokinin antagonists in the rat

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Abstract
SUMMARY: The gastric acid inhibitory activities of a peptide‐like gastrin receptor antagonist, Boc‐βAla‐Trp‐Leu‐Asp‐O(CH2)2‐Ph‐4‐F (CH‐486), a non‐peptide gastrin/CCK‐B antagonist (L‐365,260), and a CCK‐A antagonist (L‐364,718), were investigated in the gastric lumen‐perfused anaesthetized rat. A single i.v. injection of CH‐486, 100 μmol/kg, reduced acid secretion stimulated by pentagastrin, 15 μg kg/h, to unstimulated levels, with no recovery within 50 min. Histamine‐, 0.1 μmol kg/min, and carbamylcholine‐, 0.1 mg kg/h, stimulated acid secretion were also reduced to unstimulated levels by CH‐486, 100 μmol/kg, although with these latter two stimulants the inhibition was transient. L‐365,260 and L‐364,718, 10 μmol/kg, significantly inhibited both pentagastrin‐ and histamine‐stimulated acid secretion, the latter again transiently. We conclude that the non‐selective nature of the gastric acid inhibitory activity of gastrin antagonists might allow novel approaches to control gastric acid secretion in peptic ulcer disease.