I. Bakke et al., Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia, J MOL ENDOC, 25(1), 2000, pp. 109-119
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.