H3组胺受体激动剂抑制胆汁增长BDL老鼠的差别,对这些cAMP-dependent PKA / ERK1/2 / ELK-1通路。
文章的细节
-
引用
复制到剪贴板 -
弗朗西斯•H Franchitto,上野Y,格拉泽年代,DeMorrow年代,文特尔J,高迪奥E,阿尔瓦罗·D,蚕豆G, Marzioni M, Vaculin B, Alpini G
H3组胺受体激动剂抑制胆汁增长BDL老鼠的差别,对这些cAMP-dependent PKA / ERK1/2 / ELK-1通路。
实验室投资。2007年5月,87 (5):473 - 87。Epub 2007 3月5。
- PubMed ID
-
17334413 (在PubMed]
- 文摘
-
组胺调节许多函数绑定到四组胺G-coupled受体蛋白(H1R、H2R H3R和H4R)。作为H3R施加其影响通过耦合Galpha (i / o)蛋白质减少腺苷3 ',5 '一磷酸(营)水平(一个关键球员的调制cholangiocyte增生/损坏),我们评估的角色H3R调节胆汁的增长。我们提出了以下问题:(1)cholangiocytes表达H3R吗?(2)体内管理(R) -(α)- (-)-methylhistamine dihydrobromide (RAMH) (H3R受体激动剂)、马来酸thioperamide (H3R拮抗剂)或组胺,在缺乏/马来酸thioperamide,胆管结扎(BDL)老鼠调节cholangiocyte扩散?和(3)RAMH抑制cholangiocyte扩散cAMP-dependent磷酸化的差别,对这些基因的蛋白激酶A (PKA) /细胞外signal-regulated激酶1/2 (ERK1/2) / ets-like基因1 (Elk-1) ?H3R的表达是评估在肝脏的部分通过免疫组织化学和免疫荧光,通过实时PCR cholangiocyte RNA从正常和BDL老鼠。BDL老鼠(BDL)后立即治疗日常与RAMH thioperamide顺丁烯二酸盐或组胺在没有/马来酸thioperamide 1星期。与RAMH BDL体内治疗后大鼠1周,和体外刺激BDL cholangiocytes RAMH,我们评估cholangiocyte增殖,营水平和PKA, ERK1/2 Elk-1磷酸化。从正常和Cholangiocytes BDL老鼠表达H3R。H3R mRNA的表达增加BDL cholangiocytes比较正常。 Histamine decreased cholangiocyte growth of BDL rats to a lower extent than that observed in BDL RAMH-treated rats; histamine-induced inhibition of cholangiocyte growth was partly blocked by thioperamide maleate. In BDL rats treated with thioperamide maleate, cholangiocyte hyperplasia was slightly higher than that of BDL rats. In vitro, RAMH inhibited the proliferation of BDL cholangiocytes. RAMH inhibition of cholangiocyte growth was associated with decreased cAMP levels and PKA/ERK1/2/Elk-1 phosphorylation. Downregulation of cAMP-dependent PKA/ERK1/2/Elk-1 phosphorylation (by activation of H3R) is important in the inhibition of cholangiocyte growth in liver diseases.