Zabetian C P, Staley J K, Flynn D D, Mash D C
Department of Neurology, University of Miami School of Medicine, Florida 33136.
Life Sci. 1994;55(20):PL389-95. doi: 10.1016/0024-3205(94)00322-x.
The binding characteristics of the sigma-1 selective benzomorphan [3H]-(+)-pentazocine were determined in human cerebellar membranes. Saturation binding analysis revealed two affinity sites with a KDH of 1.4 +/- 0.7 nM and a KDL of 33.6 +/- 11.9 nM. Kinetic studies performed at 25 degrees C demonstrated reversible binding with association and dissociation rate constants determined for two classes of sites. In saturation binding studies, the addition of (+)-SKF 10,047 occluded binding of [3H]-(+)-pentazocine to high affinity sigma binding sites. The affinity profile of ligands displacing [3H]-(+)-pentazocine was consistent with the labeling of sigma-1 recognition sites with haloperidol > (+)-pentazocine > (+)-SKF 10,047 > (+)-3-PPP > DTG > (-)-pentazocine > (-)-SKF 10,047. The potency of the putative D3 receptor-selective ligand (+)-7-OH-DPAT was close to that measured for (+)-pentazocine in displacement experiments. These data suggest that [3H]-(+)-pentazocine labels sigma-1 sites in human cerebellum under appropriate assay conditions.
在人小脑膜中测定了σ-1选择性苯并吗啡烷[3H]-(+)-喷他佐辛的结合特性。饱和结合分析显示有两个亲和位点，KD H为1.4±0.7 nM，KD L为33.6±11.9 nM。在25℃下进行的动力学研究表明结合是可逆的，并确定了两类位点的结合和解离速率常数。在饱和结合研究中，加入(+)-SKF 10,047可阻断[3H]-(+)-喷他佐辛与高亲和力σ结合位点的结合。取代[3H]-(+)-喷他佐辛的配体的亲和力谱与用氟哌啶醇>(+)-喷他佐辛>(+)-SKF 10,047>(+)-3-PPP>DTG>(-)-喷他佐辛>(-)-SKF 10,047标记σ-1识别位点一致。推定的D3受体选择性配体(+)-7-OH-DPAT在置换实验中的效力与(+)-喷他佐辛测得的效力相近。这些数据表明，在适当的测定条件下，[3H]-(+)-喷他佐辛可标记人小脑中的σ-1位点。
