Halaris A, Piletz J E
University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Ann N Y Acad Sci. 2003 Dec;1009:1-20. doi: 10.1196/annals.1304.001.
The cardiovascular relevance of imidazoline receptors (IR) has received tremendous attention since their discovery in 1984. However, evidence also has accumulated for the relevance of IR and an endogenous ligand, agmatine, to psychiatric disease. Emphasis has been placed on altered levels of the I(1)-imidazoline site on human platelets and in human postmortem brain tissue from depressed patients. Attempts at exploring the molecular nature of the I(1) protein have led to the cloning of a protein, IRAS. Based on transfection studies, IRAS seems to be involved in neuronal plasticity events. The I(2) site also appears linked to psychiatric research since some of these sites are localized to a specific domain on monoamine oxidases. Different peptides have been identified by means of an imidazoline-receptor-binding-protein (IRBP) antiserum, and these peptides, some of which appear to be fragments derived from IRAS, undergo changes in platelets and brain commensurate with altered mood states of the subject, notably depressive symptomatology. The search for an endogenous ligand for imidazoline receptor(s) also has led to agmatine, a decarboxylated derivative of arginine. Research on agmatine has mushroomed over the past several years and its measurement in the blood and brain has opened new research opportunities. This novel neurotransmitter interacts with a variety of receptors and has been implicated in mediation of stress responses, analgesia, drug addiction and withdrawal, convulsions, and neuroprotection. Given that IR and agmatine appear involved in a multitude of neurophysiologic and pathologic functions, the potential for new drug development is intriguing.
自1984年咪唑啉受体（IR）被发现以来，其与心血管的相关性受到了极大关注。然而，关于IR及其内源性配体胍丁胺与精神疾病相关性的证据也在不断积累。重点在于抑郁症患者的人类血小板和死后脑组织中I(1)-咪唑啉位点水平的改变。对I(1)蛋白分子性质的探索尝试导致了一种名为IRAS的蛋白的克隆。基于转染研究，IRAS似乎参与神经元可塑性事件。I(2)位点似乎也与精神疾病研究相关，因为其中一些位点定位于单胺氧化酶的特定结构域。通过咪唑啉受体结合蛋白（IRBP）抗血清已鉴定出不同的肽，这些肽中的一些似乎是IRAS衍生的片段，它们在血小板和大脑中的变化与受试者情绪状态的改变相适应，尤其是抑郁症状。对咪唑啉受体的内源性配体的寻找也引出了胍丁胺，一种精氨酸的脱羧衍生物。在过去几年中，关于胍丁胺的研究迅速增加，其在血液和大脑中的测量开辟了新的研究机会。这种新型神经递质与多种受体相互作用，并与应激反应、镇痛、药物成瘾和戒断、惊厥及神经保护的介导有关。鉴于IR和胍丁胺似乎参与多种神经生理和病理功能，新药开发的潜力令人感兴趣。
