Role of histamine in the cell turnover changes associated with experimental gastric ulceration in the mastomys.
Using an animal model of gastric ulceration, in vivo and in vitro methods were developed to assess the importance of histamine in the cell turnover abnormalities previously found to occur in the preulcerous phase of gastric ulceration induced by mucosal anaphylaxis, and by using specific H1- and H2-receptor agonists and antagonists to define which receptors were involved. In ovalbumin-immunized animals, intramucosal ovalbumin injection led to a highly significant increase in cell turnover as measured by [3H]thymidine uptake (p less than 0.001). This increase was not affected by treatment with the H2 antagonist cimetidine, but was significantly reduced by the H1 antagonists promethazine and clemastine (p less than 0.01). A cell culture method was then used to examine the effects of added histamine and its antagonists. Histamine at a concentration of 10(-7) M was found to have a significant stimulatory effect on cell proliferation (p less than 0.001), and this effect was blocked by promethazine and clemastine but not by cimetidine. In contrast, histamine at a concentration of 10(-2) M had an inhibitory effect on cell proliferation which was accentuated by cimetidine and partially reversed by promethazine and clemastine. The H1 agonist betahistine was found to have stimulatory effects similar to those of histamine in low concentration (10(-7) M and 10(-6) M), but the H2 agonist 4-methyl histamine did not affect thymidine uptake at these concentrations. Both H1 and H2 agonists had a similar inhibitory effect at a concentration of 10(-2) M. It is concluded that histamine probably plays an important part in the changes in cell kinetics associated with gastric ulceration induced by this method, and that the trophic effects of histamine are mediated by H1-receptors. H2-receptors appear to have only a limited role in the control of cell proliferation.
André
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F
André
C
C
Cavagna
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S
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D002974:Clemastine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology / Q000502:physiology; D006636:Histamine Release; D008297:Male; D009115:Muridae / Q000378:metabolism*; D011398:Promethazine / Q000494:pharmacology; D013276:Stomach Ulcer / Q000378:metabolism* / Q000503:physiopathology; D013936:Thymidine / Q000378:metabolism
D006634:Histamine H1 Antagonists; D002927:Cimetidine; D002974:Clemastine; D011398:Promethazine; D013936:Thymidine