Mooney J J, Schatzberg A F, Cole J O, Kizuka P P, Salomon M, Lerbinger J, Pappalardo K M, Gerson B, Schildkraut J J
Neuropsychopharmacology Laboratory, Massachusetts Mental Health Center, Boston 02115.
Biol Psychiatry. 1988 Mar 15;23(6):543-59. doi: 10.1016/0006-3223(88)90002-9.
The present study examined the relationship between 24-hr urinary catecholamine (norepinephrine and epinephrine) output and measures of platelet adenylate cyclase (AC) activity in depressed patients (n = 17) and control subjects (n = 10). In both groups, significant inverse correlations were observed when 24-hr urinary catecholamine levels were examined in relation to measures of both receptor-mediated (prostaglandin D2 and alpha 2-adrenergic) and postreceptor-mediated (NaF) platelet AC enzyme activities, suggesting that circulating catecholamines may regulate platelet AC by heterologous (agonist-nonspecific) desensitization of the AC enzyme complex. Depressed patients who had favorable antidepressant responses to alprazolam had significantly higher pretreatment urinary catecholamine output and lower receptor-mediated platelet AC enzyme activities than control subjects, whereas the nonresponders did not. After 8 days of treatment with alprazolam, urinary catecholamine levels declined significantly. In responders, receptor-mediated measures of platelet AC activity increased significantly by day 8 to values comparable to those in control subjects; but similar changes were not observed in nonresponders. Prior to treatment, responders showed a strict linear relationship between receptor-mediated (prostaglandin D2) and postreceptor-mediated (NaF) stimulation of platelet AC activity through the stimulatory guanine nucleotide regulatory protein (Ns), whereas nonresponders did not. This suggests the presence of two distinct coupling interactions between platelet prostaglandin D2 receptors and the stimulatory guanine nucleotide regulatory protein in responders and nonresponders to the antidepressant effects of alprazolam prior to treatment. The authors propose that catecholamines, possibly acting through prostaglandins, may regulate platelet AC enzyme activity by heterologous desensitization occurring through postreceptor mechanisms.
本研究检测了17例抑郁症患者和10例对照者24小时尿儿茶酚胺（去甲肾上腺素和肾上腺素）排出量与血小板腺苷酸环化酶（AC）活性指标之间的关系。在两组中，当检测24小时尿儿茶酚胺水平与受体介导（前列腺素D2和α2 - 肾上腺素能）及受体后介导（氟化钠）的血小板AC酶活性指标的相关性时，均观察到显著的负相关，这表明循环儿茶酚胺可能通过AC酶复合物的异源（激动剂非特异性）脱敏作用来调节血小板AC。对阿普唑仑有良好抗抑郁反应的抑郁症患者，其治疗前尿儿茶酚胺排出量显著高于对照者，而受体介导的血小板AC酶活性则低于对照者，无反应者则不然。用阿普唑仑治疗8天后，尿儿茶酚胺水平显著下降。在有反应者中，到第8天时，受体介导的血小板AC活性指标显著升高，达到与对照者相当的值；但无反应者未观察到类似变化。治疗前，有反应者通过刺激性鸟嘌呤核苷酸调节蛋白（Ns）介导的受体介导（前列腺素D2）和受体后介导（氟化钠）刺激的血小板AC活性之间呈现严格的线性关系，而无反应者则不然。这表明在对阿普唑仑抗抑郁作用有反应者和无反应者中，治疗前血小板前列腺素D2受体与刺激性鸟嘌呤核苷酸调节蛋白之间存在两种不同的偶联相互作用。作者提出，儿茶酚胺可能通过前列腺素起作用，可通过受体后机制发生的异源脱敏作用来调节血小板AC酶活性。
