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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Imidazoleacetic acid-ribotide: An endogenous ligand that stimulates imidazol(in)e receptors
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Imidazoleacetic acid-ribotide: An endogenous ligand that stimulates imidazol(in)e receptors

机译：咪唑乙酸-核糖胺：刺激咪唑（in）e受体的内源性配体

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摘要

We identified the previously unknown structures of ribosylated imidazoleacetic acids in rat, bovine, and human tissues to be imidazole-4-acetic acid-riboticle (IAA-RP) and its metabolite, imidazole-4-acetic acid-riboside. We also found that IAA-RP has physicochemical properties similar to those of an unidentified substance(s) extracted from mammalian tissues that interacts with imidazol(in)e receptors (I-Rs). ["Imidazoline," by consensus (international Union of Pharmacology), includes imidazole, imidazoline, and related compounds. We demonstrate that the imidazole IAA-RP acts at I-Rs, and because few (if any) imidazolines exist in vivo, we have adopted the term "imidazol(in)e-Rs."] The latter regulate multiple functions in the CNS and periphery. We now show that IAA-RP (i) is present in brain and tissue extracts that exhibit I-R activity; (h) is present in neurons of brainstem areas, including the rostroventrolateral medulla, a region where drugs active at I-Rs are known to modulate blood pressure; (iii) is present within synaptosome-enriched fractions of brain where its release is Ca2+-dependent, consistent with transmitter function; (iv) produces I-R-linked effects in vitro (e.g., arachidonic acid and insulin release) that are blocked by relevant antagonists; and (v) produces hypertension when microinjected into the rostroventrolateral medulla. Our data also suggest that IAA-RP may interact with a novel imidazol(in)e-like receptor at this site. We propose that IAA-RP is a neuroregulator acting via I-Rs.
机译：我们确定了大鼠，牛和人体组织中核糖基化的咪唑乙酸的先前未知结构，为咪唑-4-乙酸核糖核酸（IAA-RP）及其代谢产物咪唑-4-乙酸核糖核苷。我们还发现，IAA-RP的理化性质类似于从哺乳动物组织中提取的，与咪唑（in）e受体（I-Rs）相互作用的未知物质。 [国际共识的药理学术语“咪唑啉”包括咪唑，咪唑啉和相关化合物。我们证明了咪唑IAA-RP在I-R上起作用，并且由于体内几乎不存在咪唑啉（如果有的话），因此我们采用了术语“咪唑（in）e-Rs”。]后者在CNS中调节多种功能。和外围。现在，我们显示IAA-RP（i）存在于具有I-R活性的大脑和组织提取物中； （h）存在于脑干区域的神经元中，包括后腹侧延髓，该区域已知在I-R处有活性的药物可调节血压； （iii）存在于大脑中富含突触体的部分，其释放依赖于Ca2 +，与递质功能一致； （iv）在体外产生被相关拮抗剂阻断的I-R连锁效应（例如花生四烯酸和胰岛素释放）； （v）当显微注射到腹侧外侧延髓时产生高血压。我们的数据还表明，IAA-RP可能与该部位的新型咪唑（in）e样受体相互作用。我们提出IAA-RP是一种通过I-R起作用的神经调节剂。

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