Galanin receptors in the rat gastrointestinal tract
Galanin receptors in the rat gastrointestinal tract
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DOI：
10.1016/j.npep.2004.12.023
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发表时间：
2005-06-01
期刊：
影响因子：
2.9
通讯作者：
Sternini, C
中科院分区：
文献类型：
--
作者：
Anselmi, L;Stella, SL;Sternini, C
甘丙肽功能由三种不同的G蛋白偶联受体介导，甘丙肽受体1（GaIR 1），GaIR 2和GaIR 3，它们激活不同的细胞内信号传导途径。在此，我们使用真实的时间RT-PCR定量胃肠道中GaIR 1、GaIR 2和GaIR 3的mRNA水平。GaIR 1和GaIR 2 mRNA在所有节段中均被检测到，其中大肠和胃中的水平分别最高。GaIR 3 mRNA水平相当低，并且主要局限于结肠。我们还研究了甘丙肽1-16，它具有高亲和力的GaIR 1和GaIR 2和低亲和力的GaIR 3对去极化诱发的Ca 2+增加在大鼠培养的肌间神经元使用Ca 2+成像的效果。肌间神经元胞内钙的变化进行了监测，使用钙敏感染料，荧光-4，共聚焦显微镜。甘丙肽1-16（1 μ M）显着抑制K+诱发的肌间神经元Ca ~（2+）的增加。总之，GalR的差异分布支持甘丙肽在胃肠道中的复杂作用是由多种受体亚型的激活引起的假设。此外，这项研究证实了功能性GalR的存在，并表明甘丙肽通过抑制涉及G（i/o）偶联的GaIR的电压依赖性钙通道来调节肌间神经元的递质释放。(c)2005爱思唯尔有限公司保留所有权利。
Galanin functions are mediated by three distinct G-protein-coupled receptors, galanin receptor 1 (GaIR1), GaIR2 and GaIR3, which activate different intracellular signaling pathways. Here, we quantified mRNA levels of GaIR 1, GaIR2 and GaIR3 in the gastrointestinal tract using real time RT-PCR. GaIR1 and GaIR2 mRNAs were detected in all segments with the highest levels in the large intestine and stomach, respectively. GaIR3 mRNA levels were quite low and mostly confined to the colon. We also investigated the effect of galanin 1-16, which has high affinity for GaIR1 and GaIR2 and low affinity for GaIR3 on depolarization-evoked Ca2+ increases in rat cultured myenteric neurons using Ca2+-imaging. Intracellular Ca2+ changes in myenteric neurons were monitored using the Ca2+ sensitive dye, fluo-4, and confocal microscopy. Galanin 1-16 (1 mu M) markedly inhibited the K+-evoked Ca2+ increases in myenteric neurons. In summary, the differential distribution of GalRs supports the hypothesis that the complex effects of galanin in the gastrointestinal tract result from the activation of multiple receptor subtypes. Furthermore, this study confirms the presence of functional GalRs and suggests that galanin modulates transmitter release from myenteric neurons through inhibition of voltage-dependent calcium channels involving a G(i/o)-coupled GaIR. (c) 2005 Elsevier Ltd. All rights reserved.