Histamine as an intermediate growth factor in genesis of gastric ECLomas associated with hypergastrinemia in mastomys.
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.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510.
I M
IM
Modlin
R R
RR
Kumar
C J
CJ
Soroka
H
H
Ahlman
O
O
Nilsson
J R
JR
Goldenring
D000818:Animals; D002276:Carcinoid Tumor / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D003533:Cyproheptadine / Q000494:pharmacology; D004759:Enterochromaffin Cells / Q000473:pathology; D005744:Gastric Acid / Q000378:metabolism; D005748:Gastric Fundus / Q000378:metabolism; D005755:Gastrins / Q000097:blood*; D006133:Growth Substances / Q000502:physiology; D006632:Histamine / Q000032:analysis / Q000502:physiology*; D009115:Muridae; D013274:Stomach Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*
D005755:Gastrins; D006133:Growth Substances; D003533:Cyproheptadine; D006632:Histamine