Gastrin and gastric enterochromaffin-like cell carcinoids in the rat.
Life-long administration (greater than or equal to 2 years) of a number of long-acting gastric acid inhibitors (including H2-receptor antagonists, omeprazole and ciprofibrate) has been associated with the development of gastric enterochromaffin-like cell (ECL cell) carcinoids in rats. It has been postulated that they are a consequence of some unique property of the longer-acting acid inhibitors. There is, however, a great deal of evidence to support the hypothesis that these gastric ECL cell carcinoids develop as a result of life-long hypergastrinaemia in rats. Several lines of investigation reported here show that gastric ECL cell hyperplasia occurs when gastrin levels are increased without the use of acid-inhibiting drugs. In rats, hypergastrinaemia developed after 4 weeks' administration of exogenous gastrin (4 micrograms/kg/h). The number of gastric ECL cells per visual field had increased to 250 compared with 180 in the controls. Long-term hypergastrinaemia, induced by partial gastric corpectomy, increased plasma gastrin levels from 200 to 800 pg/ml and the density of gastric ECL cells increased from 190 to 310 cells/visual field 10 weeks after the operation. Importantly, gastric ECL cell hyperplasia, which was produced in rats by administration of omeprazole, 14 mg/kg/day for 1 year, was fully reversible following normalization of gastrin levels. Until now, gastric ECL cell carcinoids have not been reported in studies of shorter-acting, reversible H2-receptor antagonists such as ranitidine, perhaps because the correct staining techniques (i.e. Grimelius and Sevier-Munger silver stains) have not been used.(ABSTRACT TRUNCATED AT 250 WORDS)
Carlsson
E
E
Gastrointestinal Research, AB Hässle, Mölndal, Sweden.
Havu
N
N
Mattsson
H
H
Ekman
L
L
D000818:Animals; D004759:Enterochromaffin Cells / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005755:Gastrins / Q000097:blood*; D006965:Hyperplasia; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D005755:Gastrins; D011899:Ranitidine; D009853:Omeprazole