TY - JOUR
T1 - Biologically active MK-801 and SKF-10 047 binding sites distinct from those in rat brain are expressed on human lung cancer cells
AU - Maneckjee, Rhoda
AU - Minna, John D.
PY - 1992
Y1 - 1992
N2 - 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 ~ 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 σ 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 μ and δ 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.
AB - 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 ~ 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 σ 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 μ and δ 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.
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U2 - 10.1091/mbc.3.6.613
DO - 10.1091/mbc.3.6.613
M3 - Article
C2 - 1323349
AN - SCOPUS:0027095993
SN - 1059-1524
VL - 3
SP - 613
EP - 619
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 6
ER -