Gastroprotective effect of histamine and acid secretion on ammonia-induced gastric lesions in rats.
BACKGROUND
Previous studies have shown that ammonia produced by Helicobacter pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence of histamine and gastric acid secretion on ammonia (NH4OH)-induced gastric lesions.


METHODS
The gastric mucosa in rats was exposed to NH4OH (1.5 ml of 250 mM solution) under basal conditions, after administration of histamine (1 mg/kg), urea with urease, and ranitidine (40 mg/kg subcutaneously) given alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric acid secretion and gastric luminal concentration of PGE2.


RESULTS
Application of NH4OH resulted in the formation of acute gastric lesions. This effect was accompanied by a fall in GBF, a rise in gastric pH, and a reduction in mucosal DNA synthesis. Administration of histamine 30 min prior to NH4OH reduced the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E2 (PGE2) production. Ranitidine given prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secretion. Ranitidine given prior to histamine abolished gastric acid secretion and the protective effect of histamine against NH4OH-induced damage; these effects were accompanied by a decrease in GBF, DNA synthesis, and concentration of PGE2. Pretreatment with 2% urea with urease given prior to NH4OH reduced NH4OH lesions. This effect was associated with an increase in gastric acid secretion, gastric generation of PGE2, GBF, and DNA synthesis. Ranitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection.


CONCLUSIONS
Histamine and gastric secretion exhibit a protective effect against ammonia-induced gastric lesions. This effect appears to depend upon the stimulation of gastric acid secretion and PGE2 production, and the improvement of gastric microcirculation.
Warzecha
Z
Z
Dept. of Physiology, Collegium Medicum of Jagiellonian University, Cracow, Poland.
Dembiński
A
A
Brzozowski
T
T
Ceranowicz
P
P
Pajdo
R
R
Niemiec
J
J
Drozdowicz
D
D
Mitis-Musioł
M
M
Konturek
S J
SJ
D000641:Ammonia; D000818:Animals; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects; D006632:Histamine / Q000502:physiology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000517:prevention & control*; D014508:Urea / Q000494:pharmacology; D014510:Urease / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D000641:Ammonia; D006632:Histamine; D011899:Ranitidine; D014508:Urea; D004247:DNA; D014510:Urease; D015232:Dinoprostone