Are high-affinity progesterone binding site(s) from porcine liver microsomes members of the σ receptor family?
Are high-affinity progesterone binding site(s) from porcine liver microsomes members of the σ receptor family?
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DOI：
10.1016/s0014-2999(98)00103-4
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发表时间：
1998-04-24
影响因子：
5
通讯作者：
Wehling, M
中科院分区：
文献类型：
--
作者：
Meyer, C;Schmieding, K;Wehling, M
最近从猪肝中分离纯化了细胞膜孕酮结合部位。由于孕酮被认为是一种内源性sigma(Sigma)受体配体，这些部位的药理学特征是选择性的sigma受体和多巴胺受体结合部位的配体，以及来自不同药理类别的其他药物。用放射性配体[H-3]孕酮在粗膜制剂和增溶部分中进行结合研究，以确定半数最大抑制浓度(IC50)值，并由此计算抑制常数(K-I值)。Sigma受体配体氟哌啶醇、柠檬酸卡倍他戊烷、1，3-二(2-甲苯基)胍、R(-)-N-(3-苯基-1-丙基)-1-苯基-2-氨基丙烷盐酸盐(R(-)-PPAAP HCl)或Sigma受体拮抗剂如(+)-3-(3-羟基苯基)-N-丙基哌啶盐酸盐(R(+)-PPP盐酸盐)和cis-9-[3-(3，5-dimethyl-1-piperazinyl)propyl]-9H-carbazole二盐酸盐(Rmcazole 2HCl)可抑制放射性配体的结合。抑制作用的层级与Sigma受体I类(中等亲和力的五唑碱、二苯基海因(苯妥英)不敏感)或II位点(高亲和力的Carbetapentane)并不完全相容，因此数据表明，猪肝膜中孕酮结合位点与Sigma受体结合位点超家族有关，但可能代表具有孕酮特异性的特定物种。(C)1998年爱思唯尔科学公司。
Membrane progesterone binding sites have been purified recently from pig liver. Since progesterone is considered as an endogenous sigma (sigma) receptor Ligand, these sites were characterized pharmacologically by ligands selective for sigma receptor and dopamine receptor binding sites, and by other drugs from distinct pharmacological classes. Binding studies using the radioligand [H-3]progesterone were done in crude membrane preparations and solubilized fractions to determine half-maximal inhibitory concentration (IC50) values, from which inhibitory constants (K-i values) were calculated. Radioligand binding was inhibited by the sigma receptor ligands haloperidol, carbetapentane citrate, 1,3-Di(2-tolyl)guanidine (DTG), R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2 aminopropane HCl (R(-)-PPAAP HCl), or sigma receptor antagonists like (+)-3-(3-hydroxyphenyl)-N-propylpiperidine HCl (R(+)-PPP HCl) and cis-9-[3-(3,5-dimethyl-1-piperazinyl)propyl]-9H-carbazole dihydrochloride (rimcazole 2HCl). The hierarchy of inhibitory action was not fully compatible with either sigma receptor class I (moderate affinity of pentazocine, diphenylhydantoin (phenytoin) insensitivity) or II sites (high affinity of carbetapentane), The data thus suggest that progesterone binding sites in porcine liver membranes are related to the sigma receptor binding site superfamily, but may represent a particular species with progesterone specificity. (C) 1998 Elsevier Science B.V.