FUNCTIONAL ASSESSMENT AND PARTIAL CHARACTERIZATION OF [H-3] (+)-PENTAZOCINE BINDING-SITES ON CELLS OF THE IMMUNE-SYSTEM

被引:38
作者
CARR, DJJ
DECOSTA, BR
RADESCA, L
BLALOCK, JE
机构
[1] UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,UAB STN,BIRMINGHAM,AL 35294
[2] NIDDK,MED CHEM LAB,BETHESDA,MD 20892
关键词
(+)-PENTAZOCINE; NEUROIMMUNOMODULATION; SIGMA RECEPTOR; MITOGEN-INDUCED PROLIFERATION; INTERLEUKIN-4;
D O I
10.1016/0165-5728(91)90170-C
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The existence of sigma receptors on lymphocytes and thymocytes was characterized using [H-3](+)-pentazocine. [H-3](+)-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-mu-M) affinity sites for [H-3](+)-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-(l-pyrrolidinyl)ethylamine (BD1008) > IR,2S-(+)-cis-N-(2-(3,4-dichlorophenyl)ethyl]-2-(l-pyrrolidinyl)cyclohexylamine (LR132) greater-than-or-equal-to (-)-pentazocine greater-than-or-equal-to phenazocine > (+/-)-trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulphonate (U-50,488H) = phencyclidine greater-than-or-equal-to haloperidol = 1,3-di-(o)-tolylguanidine. In competition studies with thymocytes, the rank order of potency for competing ligands is (+)-pentazocine = BD1008 greater-than-or-equal-to 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.
引用
收藏
页码:153 / 166
页数:14
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