PYY-Tag transgenic mice displaying abnormal (H+-K+)ATPase activity and gastric mucosal barrier impairment.
The mechanism by which the gastrointestinal hormones peptide YY and glucagon inhibit gastric acid secretion is largely unknown. PYY-Tag transgenic mice develop endocrine tumors in the colon that are composed mainly of peptide YY/enteroglucagon-producing L type cells. Therefore we studied the functional activity of such tumors and the gastric functions of PYY-Tag mice. Fasting and fed PYY-Tag transgenic mice and CD1 controls were assayed for circulating levels of peptide YY, glucagon, insulin, and gastrin. The gastric pH was determined and gastric samples were examined for (a) histologic appearance; (b) K(+)-stimulated p-nitrophenylphosphatase activity and [(14)C]aminopyrine accumulation of apical and tubulovesicle membranes; (c) adherent mucus determination by Alcian blue recovery; and (d) DNA/RNA/protein epithelial content and in vivo incorporation of [(3)H]thymidine into DNA. Transgenic mice showed high serum levels of peptide YY and glucagon, increased gastric pH, and a high incidence of gastric ulcers after fasting. p-Nitrophenylphosphatase activity, [(14)C] aminopyrine accumulation, and proton pump redistribution from cytoplasmic tubulovesicles to apical membranes were significantly lower in the gastric mucosa of transgenic mice compared with the controls. In addition, the adherent mucus was thinner, and [(3)H]thymidine incorporation into the DNA was decreased. The abnormal and unregulated levels of circulating peptide YY and glucagon led to gastric acid inhibition and an impairment of gastric barrier function as a result of a striking reduction in epithelial proliferation.
Laforenza
Umberto
U
Department of Experimental Medicine, Section of Human Physiology, University of Pavia, Pavia, Italy. umberto@unipv.it
Gastaldi
Giulia
G
Rindi
Guido
G
Leiter
Andrew B
AB
Cova
Emanuela
E
Marchetti
Annalisa
A
Candusso
Maria Elena
ME
Autelli
Michele
M
Orsenigo
Maria Novella
MN
Ventura
Ulderico
U
D000818:Animals; D005753:Gastric Mucosa / Q000201:enzymology* / Q000503:physiopathology; D005934:Glucagon / Q000097:blood; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D019894:Peptide YY / Q000235:genetics / Q000502:physiology*
D019894:Peptide YY; D005934:Glucagon; D017506:H(+)-K(+)-Exchanging ATPase