Effect of omeprazole-induced achlorhydria on trefoil peptide expression in the rat stomach.
BACKGROUND
Omeprazole is an inhibitor of the H+K+ ATPase of the gastric parietal cell, which is used clinically to suppress gastric acid secretion. It has also been found to inhibit gastric mucin production; however, its effects on the synthesis and secretion of the trefoil peptides, which are also expressed by mucus cells, and which play a key role in cytoprotection and epithelial repair, are unknown.


METHODS
Rats (n=8) were given either omeprazole (30 mg/kg per day; p.o.) or inert carrier for 1 week, and the effects on synthesis and peptide expression of the gastric trefoil peptides, TFF1/pS2 and TFF2/SP, were compared.


RESULTS
As expected, omeprazole treatment abolished H+ ion production with a mean gastric juice pH of 7.2 compared with 2.4 for controls. The omeprazole group had elevated total protein levels of 35-fold and TFF1/pS2 peptide levels elevated fourfold, respectively, but not TFF2/SP peptide in gastric juice, suggesting that the increased pH reduced the viscosity of adherent mucus, thereby increasing gastric juice concentrations by dissolution of adherent TFF1/pS2 and increased secretion. Concomitant with increased TFF1/pS2 secretion was a fall in predominantly antral mucosal trefoil peptide concentrations. In contrast to trefoil secretory rates, the steady-state synthesis of both TFF1/pS2 and TFF2/SP was unchanged after omeprazole treatment, implying both a large cellular pool of processed peptide and rapid secretion.


CONCLUSIONS
The increase in the concentration of TFF1/pS2 in gastric secretions during chronic omeprazole-induced achlorhydria may be important in preventing tissue injury and promoting repair in response to an increased luminal bacterial population.
Kang
B
B
Department of Medicine, University of Melbourne, Western Hospital, Footscray, Australia.
Alderman
B M
BM
Nicoll
A J
AJ
Cook
G A
GA
Giraud
A S
AS
D000126:Achlorhydria / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism*; D006133:Growth Substances / Q000096:biosynthesis*; D008297:Male; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D009853:Omeprazole; D010455:Peptides; D051381:Rats; D017208:Rats, Wistar; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3
D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D009853:Omeprazole