5-Hydroxytryptamine3-receptor blockade protects against gastric mucosal damage in rats.
Ondansetron, a specific 5-hydroxytryptamine3 (5-HT3)-blocker, injected s.c. (0.038, 0.075, 0.15 or 0.3 mg/kg) every 12 h with the fourth dose given 0.5 h before restraint at 4 degrees C (stress) or oral administration (p.o.) of 1 ml 80% ethanol, dose-dependently prevented gastric mucosal damage in female Sprague-Dawley rats (160-180 g); the animals were killed 2 or 1 h after stress or ethanol p.o., respectively. A similar pretreatment regimen with cyproheptadine (0.1, 0.25 or 0.5 mg/kg) or ketanserin (15, 30, or 75 micrograms/kg), both being 5HT2-receptor antagonists, also dose-dependently lowered the severity of stress- or ethanol-induced mucosal lesions. Only the higher doses of phenobarbitone (25 or 50 mg/kg given s.c. in a single dose 0.5 h beforehand) inhibited stress-induced gastric ulcers; however, even the lowest non-antinuclear dose (12.5 mg/kg), effectively produced CNS depression. These preliminary findings suggest that 5HT3-receptor blockade not only can antagonise stress- or ethanol-evoked gastric mucosal damage, but also may act through a peripheral mechanism.
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
C W
CW
Ogle
S C
SC
Hui
B S
BS
Qiu
K M
KM
Li
D000818:Animals; D003080:Cold Temperature; D003533:Cyproheptadine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D017294:Ondansetron / Q000627:therapeutic use*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012702:Serotonin Antagonists; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications
D012702:Serotonin Antagonists; D003533:Cyproheptadine; D000431:Ethanol; D017294:Ondansetron; D010634:Phenobarbital