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 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.
Klingensmith
M E
ME
Department of Surgery, Brigham and Women's Hospital, Boston, Mass., USA.
Neville
L J
LJ
Delpire
E
E
Wolfe
M M
MM
Soybel
D I
DI
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D017920:Antiporters / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects; D004247:DNA / Q000032:analysis; D005755:Gastrins / Q000097:blood / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
D000897:Anti-Ulcer Agents; D017920:Antiporters; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D005755:Gastrins; D011506:Proteins; D012333:RNA, Messenger; D028021:Sodium-Potassium-Chloride Symporters; D004247:DNA; D000254:Sodium-Potassium-Exchanging ATPase; D009853:Omeprazole