Somatostatin receptor regulation of gastric enterochromaffin-like cell transformation to gastric carcinoid.
BACKGROUND
Although somatostatin is recognized as an inhibitor of neuroendocrine cell secretion, its effect on cell proliferation has not been well defined. Generation of low acid and hypergastrinemia through irreversible H2-receptor blockade (loxtidine) in the African rodent mastomys results in gastric carcinoids (ECLomas) within 4 months. This study was undertaken to evaluate and characterize the precise somatostatin receptor (SSTR) subtype on the mastomys enterochromaffin-like (ECL) cell and to define its role in the regulation of ECL cell secretion and proliferation.


METHODS
A pure preparation (approximately 90%) of ECL cells was derived by a combination of pronase digestion and density gradient separation. We assessed the effect of somatostatin (10(-15) to 10(-7) mol/L) on gastrin-stimulated ECL cell histamine secretion and DNA synthesis (bromodeoxyuridine uptake). SSTR2 subtype was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using gene specific primers and mRNA isolated from normal and hypergastrinemia-induced ECLoma. The polymerase chain reaction product was confirmed by Southern analysis, subcloned, and sequenced.


RESULTS
Somatostatin inhibited both gastrin-stimulated histamine secretion (IC50, 5 x 10(-13) mol/L) and DNA synthesis (IC50, 10(-10) mol/L). SSTR2 was identified in the mastomys' brain, and both normal and tumor ECL cells and comparison of the brain and ECL cell SSTR2 nucleotide sequences revealed homology of 99%.


CONCLUSIONS
The SSTR2 is expressed by the mastomys' ECL cell and ECLoma. Receptor activation inhibits both ECL cell secretory and proliferative functions.
Borin
J F
JF
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
Tang
L H
LH
Kidd
M
M
Miu
K
K
Borteçen
K H
KH
Sandor
A
A
Modlin
I M
IM
D000818:Animals; D001483:Base Sequence; D002276:Carcinoid Tumor / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002838:Chromaffin System / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000378:metabolism; D006636:Histamine Release; D009115:Muridae; D017481:Receptors, Somatostatin / Q000235:genetics / Q000502:physiology*; D013270:Stomach / Q000166:cytology* / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*
D017481:Receptors, Somatostatin; D004247:DNA