Implications of gastric topical bioactive peptides in ammonia-induced acute gastric mucosal lesions in rats.
BACKGROUND
Ammonia, one of the pathogenic factors in Helicobacter pylori-induced mucosal injury, induces acute mucosal lesions in the rat glandular stomach.


METHODS
The effect of ammonia administered intragastrically on gastric peptides was investigated in urethane-anesthetized rats.


RESULTS
Gastric mucosal lesions were observed 5 min after 0.3% ammonia (4 ml/kg, intragastrically). Immunoreactive endothelin-1 (ET-1) and immunoreactive thyrotropin-releasing hormone (TRH) concentrations in the gastric wall decreased significantly 2 min and 5 min after ammonia, respectively. A significant increase in gastric juice immunoreactive ET-1 and TRH levels was reciprocally observed. The severity of gastric mucosal injury and changes in gastric immunoreactive ET-1 and TRH concentrations were shown to be concentration-dependent 30 min after ammonia. Atropine (5 mg/kg, intraperitoneally, -20 min) prevented ammonia-induced injury accompanied by a block of changes in gastric immunoreactive ET-1 and TRH concentrations. BQ-485 (ET(A) receptor antagonist; 2 mg/kg, subcutaneously) also abolished ammonia-induced lesions and gastric immunoreactive TRH changes.


CONCLUSIONS
These findings suggested that gastric ET-1 and TRH play a role in ammonia-induced gastric mucosal injury mediated via a muscarine and an ET(A) receptor.
Mori
S
S
Fourth Dept. of Internal Medicine, Aichi Medical University, Japan.
Kaneko
H
H
Mitsuma
T
T
Hayakawa
T
T
Yamaguchi
C
C
Uruma
M
M
D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005750:Gastric Juice / Q000737:chemistry; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000502:physiology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*; D013997:Time Factors
D000897:Anti-Ulcer Agents; D001381:Azepines; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D018727:Muscarinic Antagonists; D009842:Oligopeptides; C083116:BQ 485; D013004:Somatostatin; D013973:Thyrotropin-Releasing Hormone; D000641:Ammonia; D001285:Atropine