Rothman R B, Reid A, Mahboubi A, Kim C H, De Costa B R, Jacobson A E, Rice K C
Unit on Receptor Studies, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
Mol Pharmacol. 1991 Feb;39(2):222-32.
Equilibrium binding studies with the sigma receptor ligand [3H]1,3-di(2-tolyl)guanidine ([3H]DTG) demonstrated two high affinity binding sites in membranes prepared from guinea pig brain. The apparent Kd values of DTG for sites 1 and 2 were 11.9 and 37.6 nM, respectively. The corresponding Bmax values were 1045 and 1423 fmol/mg of protein. Site 1 had high affinity for (+)-pentazocine, haloperidol, (R)-(+)-PPP, carbepentane, and other sigma ligands, suggesting a similarity with the dextromethorphan/sigma 1 binding site described by Musacchio et al. [Life Sci. 45:1721-1732 (1989)]. Site 2 had high affinity for DTG and haloperidol (Ki = 36.1 nM) and low affinity for most other sigma ligands. Kinetic experiments demonstrated that [3H]DTG dissociated in a biphasic manner from both site 1 and site 2. DTG and haloperidol increased the dissociation rate of [3H]DTG from site 1 and site 2, demonstrating the presence of pseudoallosteric interactions. Inorganic calcium channel blockers such as Cd2+ selectively increased the dissociation rate of [3H]DTG from site 2, suggesting an association of this binding site with calcium channels.
用σ受体配体[3H]1,3 - 二（2 - 甲苯基）胍（[3H]DTG）进行的平衡结合研究表明，在豚鼠脑制备的膜中有两个高亲和力结合位点。DTG对位点1和位点2的表观解离常数（Kd）值分别为11.9和37.6 nM。相应的最大结合容量（Bmax）值分别为1045和1423 fmol/mg蛋白质。位点1对（+）-喷他佐辛、氟哌啶醇、（R）-（+）-PPP、卡贝戊烷和其他σ配体具有高亲和力，表明与Musacchio等人描述的右美沙芬/σ1结合位点相似[《生命科学》45:1721 - 1732（1989）]。位点2对DTG和氟哌啶醇具有高亲和力（Ki = 36.1 nM），对大多数其他σ配体具有低亲和力。动力学实验表明，[3H]DTG从位点1和位点2以双相方式解离。DTG和氟哌啶醇增加了[3H]DTG从位点1和位点2的解离速率，表明存在拟变构相互作用。无机钙通道阻滞剂如Cd2 +选择性地增加了[3H]DTG从位点2的解离速率，表明该结合位点与钙通道有关。
