Gastrin-mediated effects of omeprazole on rat colon mucosa

Background. Omeprazole increases circulating gastrin levels, which in turn may affect the growth and differentiation of colon mucosa. Chloride transpo rt mechanisms in normal colon were analyzed as markers for possible trophic actions of endogenous hypergastrinemia. Methods. Four groups of Fischer rats were studied for 10 days. Group 1 (bas eline) received to treatment. Group 2 received omeprazole only. Group 3 rec eived omeprazole plus vehicle. Group 4 received omeprazole plus CCK-B gastr in receptor antagonist (GRA) L740, 093 in vehicle. On day 10 serum gastrin was assayed. Colon mucosa was analysed for protein and DNA content. Semiqua ntitative Northern analysis measured levels of messenger RNA (mRNA) encodin g for key Cl- transporters: Na-K-Cl cotransporter (Cl- secretion in crypts) , Cl-/HCO3- exchanger (Cl- absorption in villi), and Na/K adenosine triphos phatase (not directly involved in Cl- transport). Results. Omeprazole increased gastrin levels, which were not altered by veh icle or GRA. Omeprazole increased protein, DNA, and Na/K adenosine triphosp hatase mRNA levels, with no effect by GM. In contrast, omeprazole decreased Na-K-Cl and Cl-/HCO3- mRNA levels, effects that were partly reversed Conclusions. Omeprazole augments growth index values of colon mucosa indepe ndent of serum gastrin. Against a background of omeprazole-induced achlorhy dria hypergastrinemia appears to influence differentiation rather than grow th of normal colon mucosa.