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  • Title: Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach.
    Author: Eissele R, Koop H, Bothe-Sandfort E, Arnold R.
    Journal: Digestion; 1992; 53(3-4):179-88. PubMed ID: 1363320.
    Abstract:
    The effects of two recently developed gastrin receptor antagonists, PD 136450 and L-365,260, on pentagastrin-stimulated acid secretion were investigated in rats. PD 136450 at a dose of 6 mg/kg s.c. (9.6 mumol) completely abolished acid secretion induced by pentagastrin. The inhibition of 18 mg/kg PD 136450 s.c. lasted for at least 8 h and was still effective after 14 days of treatment (18 mg/kg s.c. every 8 h). Acute application of L-365,260 at a dose of 3.8 mg/kg, which is equimolar (9.6 mumol) to 6 mg/kg PD 136450 reduced acid responses slightly. However, when L-365,260 was administered intravenously at a dose of 3 mg/kg, this antagonist completely abolished the pentagastrin-stimulated acid secretion. Furthermore, the effect of PD 136450 on endogenous gastric somatostatin and gastrin releases was tested in the isolated, vascularly perfused rat stomach. PD 136450 perfused at a concentration of 1 microM slightly increased somatostatin secretion after stimulation with a high dose of isoproterenol (10(-7) M). There was no effect of PD 136450 on basal or acetylcholine-stimulated gastrin secretion.
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