Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa.
The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.
Komuro
Y
Y
Department of Internal Medicine, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan.
Ichikawa
T
T
Ishihara
K
K
Saigenji
K
K
Hotta
K
K
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009077:Mucins / Q000032:analysis / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013758:Tetragastrin / Q000494:pharmacology*
D001570:Benzodiazepinones; D009077:Mucins; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C058121:L 365260