Functional assessment and partial characterization of [ 3H](+)-pentazocine binding sites on cells of the immune system

• Published in: Journal of neuroimmunology Vol. 35; no. 1; pp. 153 - 166
• Main Authors: Carr, Daniel J.J., De Costa, Brian R., Radesca, Lilian, Blalock, J.Edwin
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 01.12.1991; Amsterdam Elsevier; New York, NY
• Subjects: (+)-Pentazocine; Animals; Binding Sites; Binding, Competitive; Biological and medical sciences; Concanavalin A - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immune System - cytology; Immune System - metabolism; Immunobiology; Interleukin-2 - antagonists & inhibitors; Interleukin-4; Interleukin-4 - antagonists & inhibitors; Lymphocyte Activation; Lymphocytes - metabolism; Mice; Mice, Inbred C57BL; Mitogen-induced proliferation; Modulation of the immune response (stimulation, suppression); Neuroimmunomodulation; Pentazocine - metabolism; Sigma receptor; Spleen - cytology; Stereoisomerism; Thymus Gland - cytology; Thymus Gland - metabolism; Tritium; Interleukin-4; Mitogen-induced proliferation; Neuroimmunomodulation; (+)-Pentazocine; Sigma receptor; Interleukin 4; Mitogen; T cell receptor; Immunomodulation
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/0165-5728(91)90170-C

The existence of sigma receptors on lymphocytes and thymocytes was characterized using [ 3H](+)-pentazocine. [ 3H](+)-Pentazocine specifically labels high affinity sigma-type binding sites on T- and B-enriched lymphocyte membranes. The binding is saturable with T lymphocyte sites having a K D value of 401 ± 85 nM and B lymphocyte sites having a K D value of 302 ± 46 nM. Likewise, saturable high ( K D1 277 ± 92 nM) and low ( K D2 2.5 ± 1.2 μM) affinity sites for [ 3H](+)-pentazocine are found on thymocytes as well. In competition studies with lymphocytes, the rank order of potency for competing ligands is (+)-pentazocine = N-[2-(3,4-dichlorophenyl)ethyl]- N-methyl-2-(1-pyrolidinyl)ethylamine (BD1008) > 1 R,2 S-(+)- cis- N-(2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine (LR132 ≥ (−)-pentazocine ≥ phenazocine > (±)- trans-3,4-dichloro- N-methyl- N-[2-(1-pyrrolinyl)cyclohexyl]benzeneacetamide methanesulphonate (if(U-50,488H) = phencylidine ≥ haloperidol = 1,3-di-( o)-tolylguanidine. In competition studies with thymocytes, the rank order of potency for competing ligands is (+)-pentazocine = BD1008 ≥ phenazocine > haloperidol > 1,3-di-( o)-tolylguanidine > phencyclidine > (−)-pentazocine. These compounds were also investigated as potential regulatory molecules in mitogen-stimulated lymphocyte proliferation assays. Of the compounds tested, phencyclidine, 1,3-di-( o)-tolylguanidine, haloperidol, and (+)-pentazocine suppress concanavalin A-induced proliferation at high (10 −5 M) concentrations while (−)-pentazocine is inactive. When pokeweed mitogen or lipopolysaccharide are used, these compounds enhance or suppress lymphocyte proliferation depending on the mitogen and concentration of ligand. These results indicate a stereoselective receptor for (+)-pentazocine which is coupled to biological processes of lymphocytes.