title: Biologically active MK-801 and SKF-10,047 binding sites distinct from those in rat brain are expressed on human lung cancer cells.
abstract: We have shown previously that cultured human lung cancer cells of different histologic types express multiple opioid receptors that can regulate their growth. In this report, we show that these cells also express specific, saturable, and high-affinity binding sites (Kd approximately 1 nM) for the non-opioid phencyclidine (PCP), [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,b]cyclohepten-5,10-imine hydrogen maleate] (MK-801) and sigma N-allylnormetazocine (SKF-10,047) receptor ligands. Characterization of these binding sites showed them to be protein in nature and sensitive to the guanine nucleotide GTP. Pharmacological studies showed that (+) MK-801 and (+) SKF-10,047 competed with each other for their binding sites and also for the methadone binding site present in these cells. However, the mu and delta opioid ligands did not compete for (+) MK-801 and (+) SKF-10,047 binding sites. In addition, these binding sites on lung cancer cells appear to be distinct from the N-methyl D-aspartate/PCP receptor ionophore complex reported to be present in rat brain. MK-801 and SKF-10,047, at nM concentrations, were found to inhibit the growth of these cells in culture within a few hours of exposure, and this effect was irreversible after 24 h. The growth effects of these ligands could not be reversed by the opioid antagonist naloxone, suggesting involvement of nonopioid type receptors in the actions of these ligands. The abundant expression of biologically active MK-801 and SKF-10 047 binding sites in these cell lines, distinct from those in rat brain, suggests that these cell lines may prove to be a valuable source for further characterization and purification of these binding sites.
authors.affiliation: NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, Bethesda, Maryland 20889.
authors.forename: R
authors.initials: R
authors.lastname: Maneckjee
authors.forename: J D
authors.initials: JD
authors.lastname: Minna
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
chemical_list: D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine