Mucosal protective action of histamine against gastric lesions induced by HCl in rats: importance of antigastric motor activity mediated by H2-receptors.
The present study was undertaken to investigate the possible mechanism of histamine cytoprotection against 0.6 N HCl-induced gastric lesions in rats by 1) examining functional alterations such as acid secretion, gastric motor activity and mucosal vascular permeability in response to histamine and by 2) comparing the effects of histamine with those of 2-(2-pyridil)-ethylamine (PEA), an H1-agonist and of dimaprit, an H2-agonist. Histamine (3-20 mg/kg s.c.) dose-dependently increased acid secretion, inhibited motor activity and reduced the mucosal lesions in response to 0.6 N HCl. Similar effects were observed dose-dependently with dimaprit (10-40 mg/kg s.c.), but not with PEA (10 mg/kg s.c.). The protective action of both histamine and dimaprit was attenuated significantly by cimetidine (100 mg/kg s.c.) and indomethacin (5 mg/kg s.c.), but not by tripelennamine (10 mg/kg s.c.), which by itself inhibited significantly motor activity and the lesions. Stimulation of acid secretion caused by histamine as well as dimaprit was antagonized significantly by cimetidine, whereas antigastric motor effects of these agents were decreased significantly by both cimetidine and indomethacin. Histamine and PEA increased significantly the vascular permeability as measured by Evans blue, but the increased vascular permeability caused by 0.6 N HCl was reduced markedly by both histamine and dimaprit. These results suggest that the mucosal protective action of histamine may be mediated at least partly by endogenous prostaglandins through stimulation of H2-receptors, and may be associated with the effect on gastric motor activity but not with that on the mucosal vasculature.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Okada
M
M
Okabe
S
S
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006851:Hydrochloric Acid / Q000633:toxicity*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000494:pharmacology; D014309:Tripelennamine / Q000494:pharmacology
D011725:Pyridines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D014309:Tripelennamine; D002927:Cimetidine; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine; D013890:Thiourea; D006851:Hydrochloric Acid; D007213:Indomethacin; D017259:Dimaprit