Mantyh P W, Rogers S D, Ghilardi J R, Maggio J E, Mantyh C R, Vigna S R
Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417, USA.
Brain Res. 1996 May 6;719(1-2):8-13. doi: 10.1016/0006-8993(96)00050-9.
Recent pharmacological and biochemical studies have suggested that there may be more than one molecular form of the neurokinin-1 receptor (NK-1), a long and short isoform differing in the length of their cytoplasmic carboxyl-terminal tails, but no definitive evidence of the existence of such NK-1 receptor isoforms in tissue has been presented. To examine whether these different isoforms are expressed in vivo we have compared the distribution of high affinity substance P (SP) binding sites (visualized by autoradiography with [125I]SP), with the distribution of the C-terminal epitope of the full length receptor (visualized with a specific antibody against the extreme C-terminal sequence). The former method labels both long and short forms of the NK-1 receptor, while the latter labels only the long form of the protein. In the rat there is a close correspondence of [125I]SP binding and NK-1 immunoreactivity in the striatum, suggesting that the long isoform predominates in this tissue. In the parotid and submaxillary gland, there are very high levels of [125I]SP binding but only low levels of NK-1 immunoreactivity, suggesting that expression of the short form predominates in these tissues. These results imply that different tissues express different ratios of the two isoforms of the NK-1 receptor. This differential expression provides the theoretical basis for tissue specific pharmacological targeting of NK-1 receptors.
最近的药理学和生物化学研究表明，神经激肽-1受体（NK-1）可能存在不止一种分子形式，即一种长亚型和一种短亚型，它们的细胞质羧基末端尾巴长度不同，但尚未有确凿证据表明组织中存在此类NK-1受体亚型。为了研究这些不同的亚型在体内是否表达，我们比较了高亲和力P物质（SP）结合位点的分布（通过用[125I]SP进行放射自显影来可视化）与全长受体C末端表位的分布（用针对极端C末端序列的特异性抗体来可视化）。前一种方法标记NK-1受体的长亚型和短亚型，而后一种方法仅标记该蛋白的长亚型。在大鼠中，纹状体中[125I]SP结合与NK-1免疫反应性密切对应，表明长亚型在该组织中占主导。在腮腺和颌下腺中，[125I]SP结合水平非常高，但NK-1免疫反应性水平很低，表明短亚型的表达在这些组织中占主导。这些结果意味着不同组织表达NK-1受体两种亚型的比例不同。这种差异表达为NK-1受体的组织特异性药理学靶向提供了理论基础。
