Voltage-operated calcium channels in small cell lung carcinoma cell lines: pharmacological, functional, and immunological properties.
Different subtypes of voltage-operated calcium channels (VOCCs) are expressed in different tissues and can be distinguished by functional and pharmacological criteria. One type of high voltage-activated calcium channel, specifically recognized by the peptide neurotoxin omega-conotoxin (omega CTx), is expressed only in neurons. Seven different human small cell lung carcinoma (SCC) cell lines were also found to bind 125I-omega CTx. The binding was specific, saturable, and of high affinity. 125I-omega CTx binding was not antagonized by the calcium channel ligands verapamil, nitrendipine, and diltiazem. There was a correlation between the amount of toxin binding and the detection of depolarization-induced calcium fluxes studied with the fluorimetric probe Fura2. Fura2 experiments also demonstrated that, in addition to omega CTx-sensitive calcium channels, SCC cell lines also expressed omega CTx-insensitive calcium channels, which were antagonized by nitrendipine and verapamil. 125I-omega CTx-labeled VOCCs from SCC cells were, furthermore, precipitated by anti-VOCC autoantibodies obtained from patients affected by the Lambert-Eaton myasthenic syndrome, a neuromuscular disease often associated with SCC. The present findings further indicate the presence of neuronal molecules with important biological function on SCC plasma membrane and add new insights into the pathogenetic mechanism of autoimmune neurological paraneoplastic diseases, like Lambert-Eaton myasthenic syndrome.
Sher
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Department of Medical Pharmacology, University of Milano, Italy.
Pandiella
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A
Clementi
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F
D001665:Binding Sites; D001667:Binding, Competitive; D015220:Calcium Channels / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000032:analysis / Q000378:metabolism*; D020916:Conotoxins; D006801:Humans; D008175:Lung Neoplasms / Q000032:analysis / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D020916:Conotoxins; D010456:Peptides, Cyclic; C046101:conotoxin GIII; D009568:Nitrendipine; D014700:Verapamil