Gastrin-dependent inhibitory effects of octreotide on the genesis of gastric ECLomas.
BACKGROUND
The efficacy of octreotide in the regulation of endocrine tumor secretion and symptomatology has been well documented. Its effects on neuroendocrine tumor generation and cell proliferation are less well understood. The purpose of this study was to determine if blockade of somatostatin receptors by octreotide would alter gastrin levels and influence enterochromaffin-like (ECL) cell proliferation.


METHODS
The well-established gastric ECLoma model of the rodent, mastomys, was used. Animals received loxtidine (1 mg/kg/day), an irreversible H2 blocker, and subcutaneous slow release, octreotide pellet implants (150 or 300 micrograms/kg/day) or placebo pellets for a 4-month period.


RESULTS
Control parameters for gastric mucosal thickness, plasma gastrin level, ECL cell density, and bromodeoxyuridine-positive cells were 517 +/- 20 microns, 46.1 +/- 11.4 pmol/L, 7.4 +/- 0.9 cells/visual field, and 13.8 +/- 2.6 cells/visual field, respectively. After loxtidine-placebo treatment all values were significantly increased (p < 0.05; 883 +/- 70 microns, 192.8 +/- 10.6 pmol/L, 97 +/- 16.2 cells/visual field, and 51.7 +/- 19.2 cells/visual field, respectively). High dose octreotide significantly inhibited all parameters (668 +/- 3.5 microns, 66.2 +/- 20.5 pmol/L, 37.0 +/- 8.0 cells/visual field, and 10.9 +/- 2.2 cells/visual field; p < 0.05). Low dose octreotide failed to significantly inhibit ECL cell density mucosal thickness, or cell proliferation.


CONCLUSIONS
Irreversible H2 receptor blockade results in hypergastrinemia and ECL cell tumor generation. Hypergastrinemia, ECL cell hyperplasia, and cell proliferation are significantly inhibited by in vivo blockade of somatostatin receptors by administration of octreotide.
Department of Surgery, Yale University School of Medicine, New Haven, CT 06510.
I M
IM
Modlin
R
R
Kumar
A
A
Nangia
C J
CJ
Soroka
D
D
Pasikhov
J R
JR
Goldenring
D000818:Animals; D001973:Bromodeoxyuridine; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004759:Enterochromaffin Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005755:Gastrins / Q000097:blood / Q000502:physiology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006965:Hyperplasia; D008297:Male; D009115:Muridae; D015282:Octreotide / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects* / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology / Q000517:prevention & control*; D014230:Triazoles / Q000494:pharmacology
D005755:Gastrins; D006635:Histamine H2 Antagonists; D014230:Triazoles; C039993:loxtidine; D001973:Bromodeoxyuridine; D015282:Octreotide