1,3-二(2-[5-³H]甲苯基)胍与大鼠心脏膜制剂中σ2结合位点的相互作用。

Interaction of 1,3-di(2-[5-3H]tolyl) guanidine with sigma 2 binding sites in rat heart membrane preparations.

作者信息

Dumont M, Lemaire S

机构信息

Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, Canada.

出版信息

Eur J Pharmacol. 1991 Dec 17;209(3):245-8. doi: 10.1016/0014-2999(91)90176-q.

DOI:10.1016/0014-2999(91)90176-q

PMID:1665796

Abstract

Membrane preparations of rat hearts displayed specific binding activity for the prototypic sigma (sigma) receptor ligand, 1,3-di(2-[5-3H]tolyl) guanidine [( 3H]DTG), but not for the phencyclidine (PCP) receptor ligand, [3H]MK-801. Scatchard plot analysis of [3H]DTG binding revealed the presence of one high affinity saturable binding site with a KD of 8.7 nM and a Bmax of 100 pmol/g protein. The drug specificity profile of the receptor correlated with that of the sigma receptor with the following order of potency: DTG greater than haloperidol greater than (-)-pentazocine greater than (-)-butaclamol greater than (+)-butaclamol greater than (-) SKF-10047 greater than (+)pentazocine greater than PCP greater than TCP greater than MK-801 greater than (+)SKF-10047. [3H]DTG binding was sensitive to the Ca2+ channel blocker, verapamil (Ki 202 nM) but not to the K+ channel blocker, 4-aminopyridine. The reverse stereoselectivity of [3H]DTG binding for (-)-SKF-10047 and (-)-pentazocine (Ki of 1289 and 140 nM as compared with 17,582 and 2190 nM for (+)-SKF-10047 and (+)-pentazocine, respectively) indicated that the heart contains sigma receptors with characteristics of the sigma 2 subtype.

摘要

大鼠心脏的膜制剂对典型的σ受体配体1,3 - 二(2 - [5 - ³H]甲苯基)胍[(³H]DTG)表现出特异性结合活性，但对苯环己哌啶(PCP)受体配体[³H]MK - 801没有结合活性。对[³H]DTG结合进行Scatchard图分析显示存在一个高亲和力的可饱和结合位点，解离常数（KD）为8.7 nM，最大结合容量（Bmax）为100 pmol/g蛋白质。该受体的药物特异性谱与σ受体的谱相关，其效价顺序如下：DTG＞氟哌啶醇＞(-)-喷他佐辛＞(-)-布他拉莫＞(+)-布他拉莫＞(-)SKF - 10047＞(+)-喷他佐辛＞PCP＞TCP＞MK - 801＞(+)-SKF - 10047。[³H]DTG结合对钙通道阻滞剂维拉帕米敏感（抑制常数Ki为202 nM），但对钾通道阻滞剂4 - 氨基吡啶不敏感。[³H]DTG对(-)-SKF - 10047和(-)-喷他佐辛结合的反向立体选择性（(-)-SKF - 10047和(-)-喷他佐辛的Ki分别为1289和140 nM，而(+)-SKF - 10047和(+)-喷他佐辛的Ki分别为17582和2190 nM）表明心脏中含有具有σ2亚型特征的σ受体。