TY - JOUR
T1 - Gastrin-mediated effects of omeprazole on rat colon mucosa
AU - Klingensmith, Mary E.
AU - Neville, Linda J.
AU - Delpire, Eric
AU - Wolfe, M. Michael
AU - Soybel, David I.
PY - 1999
Y1 - 1999
N2 - Background. Omeprazole increases circulating gastrin levels, which in turn may affect the growth and differentiation of colon mucosa. Chloride transport 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 (baseline) received no treatment. Group 2 received omeprazole only. Group 3 received omeprazole plus vehicle. Group 4 received omeprazole plus CCK-B gastrin receptor antagonist (GRA) L740,093 in vehicle. On day 10 serum gastrin was assayed. Colon mucosa was analyzed for protein and DNA content. Semiquantitative Northern analysis measured levels of messenger RNA (mRNA) encoding for key Cl- transporters: Na-K-Cl cotransporter (Cl- secretion in crypts), Cl-/HCO3/- exchanger (Cl- absorption in villi), and Na/K adenosine triphosphatase (not directly involved in Cl- transport). Results. Omeprazole increased gastrin levels, which were not altered by vehicle or GRA. Omeprazole increased protein, DNA, and Na/K adenosine triphosphatase mRNA levels, with no effect by GRA. In contrast, omeprazole decreased Na-K-Cl and Cl-/HCO3/- mRNA levels, effects that were partly reversed by GRA. Conclusions. Omeprazole augments growth index values of colon mucosa independent of serum gastrin. Against a background of omeprazole-induced achlorhydria hypergastrinemia appears to influence differentiation rather than growth of normal colon mucosa.
AB - Background. Omeprazole increases circulating gastrin levels, which in turn may affect the growth and differentiation of colon mucosa. Chloride transport 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 (baseline) received no treatment. Group 2 received omeprazole only. Group 3 received omeprazole plus vehicle. Group 4 received omeprazole plus CCK-B gastrin receptor antagonist (GRA) L740,093 in vehicle. On day 10 serum gastrin was assayed. Colon mucosa was analyzed for protein and DNA content. Semiquantitative Northern analysis measured levels of messenger RNA (mRNA) encoding for key Cl- transporters: Na-K-Cl cotransporter (Cl- secretion in crypts), Cl-/HCO3/- exchanger (Cl- absorption in villi), and Na/K adenosine triphosphatase (not directly involved in Cl- transport). Results. Omeprazole increased gastrin levels, which were not altered by vehicle or GRA. Omeprazole increased protein, DNA, and Na/K adenosine triphosphatase mRNA levels, with no effect by GRA. In contrast, omeprazole decreased Na-K-Cl and Cl-/HCO3/- mRNA levels, effects that were partly reversed by GRA. Conclusions. Omeprazole augments growth index values of colon mucosa independent of serum gastrin. Against a background of omeprazole-induced achlorhydria hypergastrinemia appears to influence differentiation rather than growth of normal colon mucosa.
UR - http://www.scopus.com/inward/record.url?scp=0032815868&partnerID=8YFLogxK
U2 - 10.1016/S0039-6060(99)70165-0
DO - 10.1016/S0039-6060(99)70165-0
M3 - Article
C2 - 10455894
AN - SCOPUS:0032815868
SN - 0039-6060
VL - 126
SP - 272
EP - 278
JO - Surgery
JF - Surgery
IS - 2
ER -