Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder.
Platelet I1-imidazoline binding sites are elevated in depression but not generalized anxiety disorder.
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抑郁症患者的血小板 I1-咪唑啉结合位点升高，但广泛性焦虑症患者则不然。
DOI：
10.1016/0022-3956(96)00005-2
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Bari,M
中科院分区：
文献类型：
--
作者：
Piletz,JE;Halaris,A;Nelson,J;Qu,Y;Bari,M
据报道，抑郁症患者的血小板3 H-可乐定（一种α2-肾上腺素受体激动剂）结合位点密度高于正常值。奇怪的是，使用3 H-α2-拮抗剂的其他研究发现与对照组无差异。由于3 H-可乐定与血小板α2-肾上腺素受体相互作用形成G-蛋白复合物，而3 H-α2-拮抗剂与非偶联受体结合，因此G-蛋白偶联的升高可能解释了这一矛盾现象。另一种可能性是，抑郁症可能与增加非肾上腺素能I1-咪唑啉结合位点，这也是可乐定敏感。为了区分这些可能性，我们用p125 I-可乐定测定了血小板G蛋白偶联α2-肾上腺素能受体的密度（Bmax）和亲和力（KD）以及血小板I1结合位点，并比较了抑郁症（MDD）、广泛性焦虑症（GAD）和健康人的诊断组。去甲肾上腺素（NE = 10 μM）对结合的特异性抑制用于选择性定量α2-肾上腺素受体，而10 μM莫索尼定（一种> 100倍选择性I1配体）的抑制用于在NE掩蔽下定量I1结合位点。发现MDD患者的I1位点平均显著升高136%（p = 0.0007），而MDD患者的α2-肾上腺素受体Bmax值仅略有增加（p = 0.08; GAD和健康受试者无差异）。地昔帕明治疗抑郁症患者6-8周下调I1位点及α2-肾上腺素能受体两个部位也观察到正相关：（a）Bmax值与抑郁严重程度之间（使用汉密尔顿抑郁评定量表）;和（B）当合并受试者组时，治疗结束时血浆地昔帕明浓度与Bmax值下调程度之间。没有一个结合参数与血浆儿茶酚胺浓度相关。结果表明，血小板I1结合位点的密度增加可能部分解释了放射性标记可乐定作为抑郁症的潜在生物标志物的效用，尽管不能排除G蛋白偶联的额外增加。
Depressed patients have been reported to have a higher than normal density of platelet binding sites for3H-clonidine, an α2-adrenoceptor agonist. Paradoxically, other studies using3H-α2-antagonists have found no differences from controls. Because3H-clonidine interacts with platelet α2-adrenoceptors to form G-protein complexes, whereas3H-α2-antagonists bind with uncoupled receptors, an elevation in G-protein coupling might explain this paradox. Another possibility is that depression might be associated with increased non-adrenergic I1-imidazoline binding sites, which are also clonidine sensitive. To distinguish these possibilities, we utilized p125I-clonidine to measure density (Bmax) and affinity (KD) of platelet G-protein coupled α2-adrenoceptors as well as platelet I1binding sites, and compared diagnostic groups of major depressive disorder (MDD), generalized anxiety disorder (GAD) and healthy subjects. Specific inhibition of binding by norepinephrine (NE = 10 μM) was used to selectively quantify α2-adrenoceptors, whereas inhibition by 10 μM moxonidine (a > 100-fold selective I1ligand) quantified I1binding sites under a NE mask. I1sites were found to be markedly elevated by, on average, + 136% in MDD patients (p = .0007), whereas there was only a marginal increase in α2-adrenoceptor Bmaxvalues in MDD patients (p = .08; GAD and healthy subjects did not differ). Treatment of MDD patients for 6–8 weeks with desipramine downregulated I1sites as well as α2-adrenoceptors. Positive correlations were also noted for both sites: (a) between Bmaxvalues and the severity of depression (using the Hamilton Depression Rating Scale); and (b) between end-of-treatment plasma desipramine concentrations and the extent of downregulation in Bmaxvalues when subject groups were pooled. None of the binding parameters was associated with plasma catecholamine concentrations. The results suggest that an increased density of platelet I1binding sites may partially explain the utility of radiolabeled clonidine as a potential biological marker for depressive illness, although an additional increase in G-protein coupling cannot be excluded.