Cytoprotective action of histamine against 0.6 N HCl-induced gastric mucosal injury in rats; comparative study with adaptive cytoprotection induced by exogenous acid.
We examined the effects of histamine 2HCl (a stimulator of endogenous acid production) and exogenous acid on transmucosal potential difference (PD) and pH of anesthetized rat stomachs, in order to investigate the mechanism underlying the protective action of histamine against 0.6 N HCl-induced gastric mucosal injury in conscious rats. Subcutaneously administered histamine (3-20 mg/kg) dose-dependently produced a decrease in the PD and pH, and it reduced the severity of gastric mucosal injury caused by 0.6 N HCl. Both indomethacin (5 mg/kg, s.c.) and cimetidine (100 mg/kg, s.c.) completely reversed the protection afforded by histamine (20 mg/kg), although the decreased PD and pH responses were unaffected or inhibited, respectively, by indomethacin or cimetidine. Protective action of histamine was also partially mitigated by omeprazole (30 mg/kg, s.c.) which completely abolished histamine-induced acid secretion. On the other hand, exposure of the stomach for 10 min to exogenous acid (0.1-0.35 N HCl) caused a PD reduction and an increase of pH, in a concentration-related manner. The injury caused by 0.6 N HCl was prevented by prior exposure to these low concentrations of HCl, and the degrees of inhibition were associated with the concentration of HCl and the magnitude of PD reduction caused by HCl. The pretreatment with indomethacin, but not cimetidine or omeprazole, significantly antagonized the increased pH and mucosal protection induced by 0.35 N HCl. These results suggest that histamine protected the gastric mucosa against 0.6 N HCl-induced injury by two different ways, mediated with endogenous prostaglandins, (a) mainly through stimulation of H2-receptors and (b) partly through adaptive cytoprotection induced by acid.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Furukawa
O
O
Okabe
S
S
D000222:Adaptation, Physiological; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006632:Histamine / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002927:Cimetidine; D006632:Histamine; D009853:Omeprazole; D006851:Hydrochloric Acid; D007213:Indomethacin