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Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand.

Publication ,  Journal Article
Campa, MJ; Schreiber, G; Bepler, G; Bishop, MJ; McNutt, RW; Chang, KJ; Patz, EF
Published in: Cancer Res
April 1, 1996

Cancer cells are often characterized by the presence of membrane receptors not normally associated with nontransformed cells from the same tissue type. Recent studies have demonstrated increased expression of high-affinity binding sites for opioid receptor-selective ligands in lung cancer cell lines relative to normal lung tissue. We investigated the binding of a nonpeptidic delta opioid receptor ligand in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells with the aim of developing the ligand as a novel lung cancer imaging agent. The ligand, [3H] (+)-4-[alpha-R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide ([3H](+)BW373U86), bound with high-affinity [Kd (dissociation constant) = 0.066 +/- 0.012 nM] to membranes prepared from six different SCLC cell lines but not to those from seven NSCLC cell lines, including one mesothelioma. The number of biding sites varied from 10 to 300 fmol/mg membrane protein. Competition binding studies demonstrated displacement of [3H](+)BW373U86 binding by the delta-selective antagonists naltriben and 7-benzylidenenaltrexone but not with the mu- and kappa- selective antagonists D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]ben zeneacetamide methanesulfonate. Mean apparent Kis for naltriben and 7-benzylidenenaltrexone in membranes from two SCLC cell lines were 0.17 and 3.9 nM, respectively, but were >10 microM for the mu and kappa ligands. The nonselective antagonist naloxone displaced [3H](+)BW373U86 binding with an apparent Ki of approximately 29 nM. On the basis of these data, we believe the lung cancer receptor to be similar, if not identical, to the human brain delta opioid receptor. The lack of high-affinity [3H](+)BW373U86 binding in normal mouse lung membranes suggests a potential role for this ligand as a novel therapeutic or imaging agent.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 1996

Volume

56

Issue

7

Start / End Page

1695 / 1701

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Opioid, delta
  • Piperazines
  • Oncology & Carcinogenesis
  • Mice
  • Lung Neoplasms
  • Lung
  • Humans
  • Carcinoma, Small Cell
  • Binding, Competitive
 

Citation

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Campa, M. J., Schreiber, G., Bepler, G., Bishop, M. J., McNutt, R. W., Chang, K. J., & Patz, E. F. (1996). Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand. Cancer Res, 56(7), 1695–1701.
Campa, M. J., G. Schreiber, G. Bepler, M. J. Bishop, R. W. McNutt, K. J. Chang, and E. F. Patz. “Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand.Cancer Res 56, no. 7 (April 1, 1996): 1695–1701.
Campa MJ, Schreiber G, Bepler G, Bishop MJ, McNutt RW, Chang KJ, et al. Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand. Cancer Res. 1996 Apr 1;56(7):1695–701.
Campa, M. J., et al. “Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand.Cancer Res, vol. 56, no. 7, Apr. 1996, pp. 1695–701.
Campa MJ, Schreiber G, Bepler G, Bishop MJ, McNutt RW, Chang KJ, Patz EF. Characterization of delta opioid receptors in lung cancer using a novel nonpeptidic ligand. Cancer Res. 1996 Apr 1;56(7):1695–1701.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

April 1, 1996

Volume

56

Issue

7

Start / End Page

1695 / 1701

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Receptors, Opioid, delta
  • Piperazines
  • Oncology & Carcinogenesis
  • Mice
  • Lung Neoplasms
  • Lung
  • Humans
  • Carcinoma, Small Cell
  • Binding, Competitive