Gastrin receptor expression and function during rapid transformation of the enterochromaffin-like cells in an African rodent.
The enterochromaffin-like cell (ECL) cells of the stomach are principally regulated by gastrin via a gastrin/CCK(B) receptor (G[R]) which modulates both histamine secretion and cell proliferation. In the African rodent (mastomys) hypergastrinemia generated by the histamine-2 receptor antagonist (loxtidine) results in ECL cell hyperplasia and neoplasia at 8 and 16 weeks respectively. The expression, structure and function of the G(R) during transformation is however unknown. We utilized a pure (approximately 90%) preparation of ECL cells to evaluate alterations in the G(R) utilizing immunocytochemistry, Western blot analysis, reverse transcription polymerase chain reaction (RT-PCR), 5-bromo-2-deoxyuridine uptake and phosphorylation site analysis. Although the expression of ECL cell G(R) was upregulated at both mRNA (PT-PCR) and protein (Western analysis) level, its affinity to gastrin was decreased in the hyperplastic phase and lost during transformation. The coding sequence of the G(R) of mastomys tumor ECL cells was identical to that of normal ECL cells, parietal cells and the brain. However, the mRNA sequence of the third introcytoplasmic loop of the G(R) was significantly different to other species. In addition, the G(R) exhibited phosphorylation site on serine residue(s). We have thus noted a direct correlation between hypergastrinemia and G(R) alteration and function during ECL cell transformation. It is possible that the unique mastomys gastrin receptor mediated ECL cell transformation involves the novel phosphorylation sites and a divergence in the introcytoplasmic domain.
Tang
L H
LH
Department of Surgery, Yale University School of Medicine, and the Department of Veterans Affairs Medical Center, New Haven, CT 06520, USA.
Luque
E A
EA
Efstathiou
J A
JA
Bortecen
K H
KH
Kidd
M
M
Tarasova
N I
NI
Modlin
I M
IM
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D004759:Enterochromaffin Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005755:Gastrins / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009115:Muridae; D010766:Phosphorylation; D010768:Phosphoserine / Q000032:analysis / Q000378:metabolism; D019000:Phosphotyrosine / Q000032:analysis / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011949:Receptors, Cholecystokinin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology
D005755:Gastrins; D006635:Histamine H2 Antagonists; D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D014230:Triazoles; D010768:Phosphoserine; D019000:Phosphotyrosine; C039993:loxtidine