Gastric neuroendocrine cell hyperplasia after treatment with the long-acting, potent H2-receptor antagonist SK&F 93479.
The time course and dose response of the neuroendocrine cell hyperplasia in the oxyntic mucosa of the rat was examined after treatment with the potent, long-acting H2-receptor antagonist SK&F 93479 at doses of 0 and 1000 mg/kg orally for 1, 3, 7, and 14 days and at doses of 0, 40, 200, and 1000 mg/kg orally for 1 and 6 months. The number of oxyntic neuroendocrine cells (chromogranin-positive) increased after 7 days of treatment. In the 1- and 6-month studies with doses of 1000 mg/kg, the grading for the number of oxyntic chromogranin-positive cells was 2.5 to 3 times the control levels, and they were distributed mostly throughout the mucosa, whereas at lower doses, which did not produce carcinoid tumours at 2 years, the neuroendocrine cells were distributed in the lower half of the mucosa with 1.5- to 2-fold increases in grades for cell numbers. Increases in cell numbers and cell distribution may be useful factors in the evaluation of the neuroendocrine cell hyperplasia found in, for example, the Zollinger-Ellison syndrome and chronic atrophic gastritis, in which hypergastrinaemia and fundic neuroendocrine cell hyperplasia are present.
D000818:Animals; D002864:Chromogranins; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D009490:Neurosecretory Systems / Q000473:pathology*; D011744:Pyrimidinones / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D002864:Chromogranins; D006635:Histamine H2 Antagonists; D011744:Pyrimidinones; C033275:SK&F 93479