Borin J F, Tang L H, Kidd M, Miu K, Borteçen K H, Sandor A, Modlin I M
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
Surgery. 1996 Dec;120(6):1026-32. doi: 10.1016/s0039-6060(96)80050-x.
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.
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.
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%.
The SSTR2 is expressed by the mastomys' ECL cell and ECLoma. Receptor activation inhibits both ECL cell secretory and proliferative functions.
尽管生长抑素被认为是神经内分泌细胞分泌的抑制剂，但其对细胞增殖的影响尚未明确界定。通过在非洲啮齿动物马斯托鼠中进行不可逆的H2受体阻断（洛昔丁）产生低酸血症和高胃泌素血症，会在4个月内导致胃类癌（肠嗜铬样细胞肿瘤）。本研究旨在评估和鉴定马斯托鼠肠嗜铬样（ECL）细胞上确切的生长抑素受体（SSTR）亚型，并确定其在调节ECL细胞分泌和增殖中的作用。
通过链霉蛋白酶消化和密度梯度分离相结合的方法获得了纯度约为90%的ECL细胞纯制剂。我们评估了生长抑素（10^(-15)至10^(-7)mol/L）对胃泌素刺激的ECL细胞组胺分泌和DNA合成（溴脱氧尿苷摄取）的影响。使用基因特异性引物和从正常及高胃泌素血症诱导的ECL瘤中分离的mRNA，通过逆转录-聚合酶链反应（RT-PCR）评估SSTR2亚型。聚合酶链反应产物经Southern分析确认、亚克隆并测序。
生长抑素抑制了胃泌素刺激的组胺分泌（IC50，5×10^(-13)mol/L）和DNA合成（IC50，10^(-10)mol/L）。在马斯托鼠的脑中鉴定出了SSTR2，正常和肿瘤ECL细胞以及脑和ECL细胞SSTR2核苷酸序列的比较显示同源性为99%。
SSTR2在马斯托鼠的ECL细胞和ECL瘤中表达。受体激活抑制了ECL细胞的分泌和增殖功能。
