Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.
Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.
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DOI：
10.1001/archpsyc.1988.01800270053006
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发表时间：
1988-03
影响因子：
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通讯作者：
J. Halper;Richard P. Brown;J. Sweeney;J. Kocsis;A. Peters;J. Mann
中科院分区：
文献类型：
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作者：
J. Halper;Richard P. Brown;J. Sweeney;J. Kocsis;A. Peters;J. Mann
以前的研究表明，与正常对照受试者相比，从无药物的内源性抑郁症住院患者中分离的外周血单核细胞对单一浓度异丙肾上腺素的反应减弱。我们现在报告异丙肾上腺素剂量反应研究的结果，表明在无药物的内源性抑郁症住院患者中，在10（-10）至10（-5）mol/L的浓度范围内，异丙肾上腺素刺激后，环腺苷酸基础水平较低，环腺苷酸水平降低。导致抑郁症患者环腺苷酸产生减少的主要因素是能够产生环腺苷酸的受体位点的丢失。结合我们先前报告的发现，即从抑郁症患者中获得的外周血单核细胞中β-肾上腺素能拮抗剂结合是正常的，剂量反应研究的结果表明受体功能丧失（脱敏）而不是受体结合位点数量减少（下调）是潜在机制。潜在的解释β-肾上腺素能脱敏和抑郁症的儿茶酚胺假说的影响进行了讨论。
Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.