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 fo r the gastrin cell stimulation is unknown. The somatostatin analog octreoti de LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with cipro fibrate (50 mg/kg body weight per day) alone or combined with octreotide LA R (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocr ine cell densities and mRNA abundances were measured. Ciprofibrate increase d gastrin mRNA abundance (P<0.05), gastrin cell number (<0.001) and cell ar ea (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profoun d ECL cell hyperplasia, confirmed by an increase in chromogranin A (CgA) an d histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL cel ls 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 inhib ited basal ECL cell function and growth. Ciprofibrate stimulates gastrin ce ll activity by a mechanism unaffected by octreotide, but octreotide does in hibit basal and gastrin-stimulated ECL cell function and growth.