Effect of gastrin receptor antagonists on gastric acid secretion and gastrin and somatostatin release in the rat stomach.
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.
Department of Internal Medicine, Philipps University, Marburg, FRG.
R
R
Eissele
H
H
Koop
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E
Bothe-Sandfort
R
R
Arnold
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D010418:Pentagastrin; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology*; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000378:metabolism*; D013270:Stomach / Q000187:drug effects; D013997:Time Factors
D001570:Benzodiazepinones; D005755:Gastrins; D007211:Indoles; D010627:Phenethylamines; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C077645:PD 136450; C058121:L 365260; D013004:Somatostatin; D010418:Pentagastrin