Takhshid M A, Owji A A, Vasei M, Panjehshahin M R, Tabei S M B, Tabatabaee H R, Ay J
Department of Biochemistry, The Shiraz University of Medical Sciences, P.O. Box 1971 Shiraz, Iran.
Brain Res. 2004 Sep 10;1020(1-2):30-6. doi: 10.1016/j.brainres.2004.05.112.
Adrenomedullin (AM) immunoreactivity and mRNA, in addition to a large number of specific AM-binding sites, exist in the rat spinal cord. However, no phenotype has been reported for AM in the spinal cord. Here, expression of c-fos in response to intrathecal (i.t.) administration of AM, proadrenomedullin N-terminal 20 peptide (PAMP) and calcitonin gene-related peptide (CGRP) was examined in the thoracic, lumbar and sacral regions of spinal cord in conscious rats. Two hours after i.t. administration of either CGRP (2.5 and 10 microg) or AM (10 microg), the number of c-Fos immunoreactive nuclei was increased in all the spinal regions examined in this study, with the highest increase observed in the superficial dorsal horn. Few cells with c-fos immunoreactivity were found in the spinal cord of rats 2 h after i.t. injection of either saline or PAMP. Effects of AM (10 microg) and CGRP (2.5 microg) on c-fos expression were blocked when rats were pretreated with 40 microg of intrathecal CGRP8-37 (CGRP1 receptor antagonist). Fos-like immunoreactivity induced by i.t. CGRP and/or AM were also significantly abolished by i.t. administration of the nitric oxide (NO) inhibitor, l-NAME, indicating that endogenous NO is a necessary intermediary in CGRP and AM induced c-fos expression in the rat spinal cord. In conclusion, AM induces c-fos expression in rat spinal cord when administered intrathecally, with the pattern being similar to those produced by i.t. CGRP. Effects of the two peptides are sensitive to CGRP8-37 and l-NAME.
除了大量特异性的肾上腺髓质素（AM）结合位点外，大鼠脊髓中还存在AM免疫反应性和mRNA。然而，脊髓中AM的表型尚未见报道。在此，研究了清醒大鼠脊髓胸段、腰段和骶段中，鞘内注射AM、前肾上腺髓质素N端20肽（PAMP）和降钙素基因相关肽（CGRP）后c-fos的表达情况。鞘内注射CGRP（2.5和10微克）或AM（10微克）两小时后，本研究中所有检测的脊髓区域中c-Fos免疫反应性细胞核数量均增加，在浅表背角增加最为明显。鞘内注射生理盐水或PAMP两小时后，大鼠脊髓中几乎未发现有c-fos免疫反应性的细胞。当大鼠用40微克鞘内CGRP8-37（CGRP1受体拮抗剂）预处理时，AM（10微克）和CGRP（2.5微克）对c-fos表达的影响被阻断。鞘内注射一氧化氮（NO）抑制剂L-NAME也显著消除了鞘内注射CGRP和/或AM诱导的Fos样免疫反应性，表明内源性NO是CGRP和AM诱导大鼠脊髓c-fos表达的必要中介。总之，鞘内注射AM可诱导大鼠脊髓中c-fos表达，其模式与鞘内注射CGRP产生的模式相似。这两种肽的作用对CGRP8-37和L-NAME敏感。
