Histamine as an intermediate growth factor in genesis of gastric ECLomas associated with hypergastrinemia in mastomys

Abstract

Profound and sustained inhibition of gastric acid secretion has been associated with development of carcinoid tumors of the fundic enterochromaffin-like (ECL) cells in rodents. While ECL cell hyperplasia has been recognized in humans, the development of carcinoid tumors is rare and often confined to patients under treatment for gastrinoma related to the multiple endocrine neoplasia type I (MEN1) syndrome. The Mastomys was utilized as a model for the rapid induction of ECLomas by insurmountable acid secretory blockade induced by the pharmacologically irreversible H2-receptor antagonist, loxtidine. Loxtidine-induced ECL cell hyperplasia and neoplasia were compared in the absence of presence of cyproheptadine (0.5 mg/kg), an H1-receptor antagonist. Loxtidine administration resulted in a significant increase in ECL cell hyperplasia and neoplasia as well as an increase in ECL cell number, mucosal thickness, plasma gastrin levels, and stomach weight. Cyproheptadine ameliorated loxtidine-induced ECL cell hyperplasia and neoplasia and significantly decreased loxtidine-stimulated increases in ECL cell number. Nevertheless, cyproheptadine failed to alter the loxtidine-induced increase in plasma gastrin, stomach weight or mucosal height. The results indicate that cyproheptadine, an H1-receptor antagonist, inhibits loxtidine-induced ECL cell hyperplasia independent of any effects on serum gastrin.

Expression of histidine decarboxylase in human colonic cancer cells and adenomatous polyps

“…Recent evidence has helped to clarify the function of HDC, histamine receptors and their possible involvement in cancer development. Histamine has been considered to be an important growth factor in colonic and gastric cancer as well as in melanoma [4,5].…”

Gastric Carcinoid with Histamine Production, Histamine Transporter and Expression of Somatostatin Receptors

“…Analysis of histamine in culture medium was performed by HPLC using precolumn derivatization with o-phthalaldehyde and 2-mercaptoethanol in borate buffer and fluorescence detection as previously described [12]. Samples of cell culture medium (400 Ìl) were extracted using Bond Elute columns prior to analysis.…”

Effect of a histamine H 1 receptor antagonist on gastric endocrine cell proliferation induced by chronic acid suppression in rats

“…The H 1 receptor is known to be involved in vasoconstriction 11 reported that both H 1 and H 2 receptors were expressed by G cells, and that gastrin secretion was inhibited by H 1 receptors and stimulated by H 2 receptors. Modlin et al 9 reported that histamine may also act as an autocrine growth factor for ECL hyperplasia via the H 1 receptor. Therefore, histamine may be an important regulator of all gastric endocrine cells.…”

“…Interestingly, Sandvik et al 8 reported that gastrin produced dose-dependent histamine release from ECL cells in the rat stomach. Modlin et al 9 reported that histamine H 1 receptors were expressed by ECL cells and that histamine was an autocrine growth factor for ECL cell proliferation. However, the mechanism by which histamine influences ECL cell proliferation is not still clear.…”