Halper J P, Brown R P, Sweeney J A, Kocsis J H, Peters A, Mann J J
Department of Psychiatry, Cornell University Medical College, New York, NY 10021.
Arch Gen Psychiatry. 1988 Mar;45(3):241-4. doi: 10.1001/archpsyc.1988.01800270053006.
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.
以往对从无药物治疗的内源性重度抑郁症住院患者中分离出的外周血单核细胞的研究表明，与正常对照受试者相比，单浓度异丙肾上腺素刺激下的3',5'-单磷酸腺苷（环磷酸腺苷）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，该研究表明，在无药物治疗的内源性抑郁症住院患者中，环磷酸腺苷的基础水平较低，并且在10(-10)至10(-5) mol/L浓度范围内的异丙肾上腺素刺激下，环磷酸腺苷水平也降低。抑郁症患者中环磷酸腺苷产生减少的主要因素是能够产生环磷酸腺苷的受体位点丧失。结合我们之前报道的发现，即从抑郁症患者获得的外周血单核细胞中β-肾上腺素能拮抗剂结合正常，剂量反应研究的结果表明，作为潜在机制的是受体功能丧失（脱敏）而非受体结合位点数量减少（下调）。讨论了β-肾上腺素能脱敏的潜在解释及其对抑郁症儿茶酚胺假说的影响。
