Xu Y, Kaji H, Okimura Y, Matsui T, Abe H, Chihara K
Department of Medicine, Kobe University School of Medicine, Japan.
Neuroendocrinology. 1996 Oct;64(4):280-5. doi: 10.1159/000127129.
Cholecystokinin (CCK) is detected in pituitary tumors but its role remains unknown. On the hypothesis that CCK may facilitate the cell growth in pituitary tumors, we have examined the effect of CCK on cell growth using a rat pituitary tumor cell line, GH3, cultured in a serum-free, chemically defined medium. Addition of sulfated CCK-(26-33) (CCK-8) in two different concentrations (0.5 approximately 1 nM) caused a significant increase in the number of GH3 cells. The antagonist (1 microM) for CCK-B receptor, but not CCK-A receptor, significantly inhibited the number of GH3 cells. Northern blot analysis revealed a significant expression of CCK-B receptor mRNA in GH3 cells, but not in normal rat pituitary glands. In addition, immunoreactive CCK/gastrin was detected by RIA in the GH3 cell extracts as well as the serum-free culture medium. In GH3 cell extracts, both CCK-8 and gastrin like peptides were identified by gel chromatography. These findings provided the first evidence for an autocrine/paracrine role of CCK and gastrin on stimulation of GH3 cell growth through the CCK-B receptor.
在垂体肿瘤中检测到胆囊收缩素（CCK），但其作用尚不清楚。基于CCK可能促进垂体肿瘤细胞生长的假说，我们使用在无血清、化学成分明确的培养基中培养的大鼠垂体肿瘤细胞系GH3，研究了CCK对细胞生长的影响。添加两种不同浓度（0.5至约1 nM）的硫酸化CCK-(26 - 33)（CCK-8）导致GH3细胞数量显著增加。CCK-B受体拮抗剂（1 microM）而非CCK-A受体拮抗剂，显著抑制了GH3细胞数量。Northern印迹分析显示，GH3细胞中CCK-B受体mRNA有显著表达，而正常大鼠垂体中未检测到。此外，通过放射免疫分析在GH3细胞提取物以及无血清培养基中检测到免疫反应性CCK/胃泌素。在GH3细胞提取物中，通过凝胶色谱法鉴定出CCK-8和胃泌素样肽。这些发现首次证明了CCK和胃泌素通过CCK-B受体对GH3细胞生长的自分泌/旁分泌作用。
