Risby E D, Hsiao J K, Manji H K, Bitran J, Moses F, Zhou D F, Potter W Z
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Arch Gen Psychiatry. 1991 Jun;48(6):513-24. doi: 10.1001/archpsyc.1991.01810300025004.
As part of a study of the effects of lithium carbonate on neurochemical function in man, platelet and lymphocyte adenylate cyclase activity and lymphocyte beta-adrenergic receptor binding characteristics were determined before and after 2 weeks of lithium treatment in 10 normal volunteers. Lithium had differential effects on platelet and lymphocyte adenylate cyclase activity. In platelets, basal and stimulated (guanyl imidodiphosphate [Gpp[NH]p] or cesium fluoride) adenylate cyclase activity was significantly augmented by lithium treatment. By contrast, in lymphocytes, Gpp(NH)p- and cesium fluoride-stimulated adenylate cyclase activity was unaffected, while basal activity was decreased modestly after lithium. These results are consistent with preclinical studies that suggest that lithium's effects on adenylate cyclase activity are specific with respect to tissue and brain region and that lithium may interfere with guanine nucleotide binding (G) protein function. Lithium treatment significantly increased the ratio of low- to high-affinity dissociation constants for agonist displacement of antagonist binding to lymphocyte beta-adrenergic receptors (thought to reflect coupling between the beta-adrenergic receptor and stimulatory G protein). Lithium had significant effects on measures associated with signal transduction that might be contrasted to its more subtle effects on neuronal function (norepinephrine release) and neuroendocrine systems (responses to serotoninergic challenge) in these same subjects (reported in a companion article). Lithium's primary site of action may be on signal transduction mechanisms. These effects subsequently may be manifested in changes in neurotransmitter function that may be important to lithium's mood-stabilizing actions.
作为碳酸锂对人体神经化学功能影响研究的一部分，在10名正常志愿者接受锂治疗2周前后，测定了血小板和淋巴细胞腺苷酸环化酶活性以及淋巴细胞β-肾上腺素能受体结合特性。锂对血小板和淋巴细胞腺苷酸环化酶活性有不同影响。在血小板中，锂治疗显著增强了基础和刺激（鸟苷亚氨基二磷酸[Gpp(NH)p]或氟化铯）腺苷酸环化酶活性。相比之下，在淋巴细胞中，Gpp(NH)p和氟化铯刺激的腺苷酸环化酶活性未受影响，而锂治疗后基础活性略有下降。这些结果与临床前研究一致，提示锂对腺苷酸环化酶活性的影响在组织和脑区方面具有特异性，且锂可能干扰鸟嘌呤核苷酸结合（G）蛋白功能。锂治疗显著增加了激动剂取代拮抗剂与淋巴细胞β-肾上腺素能受体结合的低亲和力与高亲和力解离常数之比（被认为反映β-肾上腺素能受体与刺激性G蛋白之间的偶联）。锂对与信号转导相关的指标有显著影响，这可能与其对这些相同受试者的神经元功能（去甲肾上腺素释放）和神经内分泌系统（对血清素能激发的反应）的更细微影响形成对比（在一篇配套文章中报道）。锂的主要作用位点可能在信号转导机制上。这些影响随后可能表现为神经递质功能的变化，这可能对锂的情绪稳定作用很重要。
