De Aizpurua H J, Lambert E H, Griesmann G E, Olivera B M, Lennon V A
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Cancer Res. 1988 Sep 1;48(17):4719-24.
The Lambert-Eaton myasthenic syndrome (LES) is an autoimmune presynaptic disorder of peripheral cholinergic neurotransmission in which there is often an associated small cell lung carcinoma (SCC). SCC lines established from patients with and without LES exhibit a Ca2+ influx response to depolarization by K+ that is consistent with the presence of voltage-gated Ca2+ channels. Autoantibodies antagonistic to SCC Ca2+ channel activity were found exclusively in patients with LES, independent of cancer status. Depolarization-induced uptake of 45Ca2+ by SCC lines was reduced maximally after 3-4 days of exposure to serum immunoglobulins from 14 of 19 LES patients, while 53 control immunoglobulins (including patients with SCC, other tumors, other paraneoplastic syndromes, and other neurological and autoimmune diseases) were without effect. The snail neurotoxin omega-conotoxin of subtype GVIA, which is a specific antagonist of presynaptic Ca2+ channels, inhibited K+-stimulated Ca2+ uptake in a dose-dependent manner that was essentially irreversible. Adenosine, reported to be a specific antagonist of neuronal Ca2+ channels, also impaired voltage-stimulated Ca2+ influx in SCC. Use of LES patients' IgG and omega-conotoxin in further studies of SCC may facilitate identification and purification of the LES antigen(s) and yield a quantitative serological test for diagnosing this autoimmune paraneoplastic syndrome.
兰伯特-伊顿肌无力综合征（LES）是一种外周胆碱能神经传递的自身免疫性突触前疾病，常伴有小细胞肺癌（SCC）。从有或无LES的患者建立的SCC细胞系表现出对K⁺去极化的Ca²⁺内流反应，这与电压门控Ca²⁺通道的存在一致。仅在LES患者中发现了对抗SCC Ca²⁺通道活性的自身抗体，与癌症状态无关。在暴露于19例LES患者中14例的血清免疫球蛋白3 - 4天后，SCC细胞系去极化诱导的⁴⁵Ca²⁺摄取最大程度降低，而53种对照免疫球蛋白（包括SCC患者、其他肿瘤患者、其他副肿瘤综合征患者以及其他神经和自身免疫性疾病患者）则无此作用。亚型为GVIA的蜗牛神经毒素ω-芋螺毒素是突触前Ca²⁺通道的特异性拮抗剂，它以剂量依赖的方式抑制K⁺刺激的Ca²⁺摄取，且基本上不可逆。据报道，腺苷是神经元Ca²⁺通道的特异性拮抗剂，它也损害SCC中电压刺激的Ca²⁺内流。在SCC的进一步研究中使用LES患者的IgG和ω-芋螺毒素可能有助于鉴定和纯化LES抗原，并产生一种用于诊断这种自身免疫性副肿瘤综合征的定量血清学检测方法。
