Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia.
The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a consequence, enterochromaffin-like (ECL) cell hyperplasia. The mechanism for the gastrin cell stimulation is unknown. The somatostatin analog octreotide LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocrine cell densities and mRNA abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05), gastrin cell number (P<0. 001) and cell area (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profound ECL cell hyperplasia, confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL cells and plasma histamine levels (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin cells, but all parameters of ECL cell hyperplasia were reduced (P<0.001). Octreotide LAR also significantly inhibited basal ECL cell function and growth. Ciprofibrate stimulates gastrin cell activity by a mechanism unaffected by octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL cell function and growth.
Bakke
I
I
Department of Physiology and Biomedical Engineering, Norwegian University of Science and Technology, Trondheim, Norway. Ingunn.Bakke@medisin.ntnu.no
Sandvik
A K
AK
Waldum
H L
HL
D000818:Animals; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000633:toxicity; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D058607:Fibric Acids; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005755:Gastrins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D015282:Octreotide / Q000494:pharmacology*; D020025:Peroxisome Proliferators / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D053379:Chromogranin A; D002864:Chromogranins; D058607:Fibric Acids; D005755:Gastrins; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D002995:Clofibric Acid; D006632:Histamine; D006640:Histidine Decarboxylase; C019304:ciprofibrate; D015282:Octreotide