DeHaven-Hudkins D L, Daubert J D, Sawutz D G, Tiberio L, Baine Y
Department of Biochemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426, USA.
Immunopharmacology. 1996 Oct;35(1):27-39. doi: 10.1016/0162-3109(96)00107-5.
The binding characteristics of the sigma ligand [3H]1.3-di(2-tolyl)guanidine (DTG) were investigated in membranes prepared from the Jurkat T cell line. Binding was saturable with a KD of 56 +/- 3 nM and a Bmax of 11706 +/- 3173 fmol/mg protein (n = 3). The rank order of potency for sigma reference compounds to inhibit binding in the Jurkat cell line was ifenprodil > 1,3-di(2-tolyl)guanidine > haloperidol > carbetapentane > (+)3-(3-hydroxyphenyl)-N-propylpiperidine ((+)3-PPP) > (-)pentazocine > caramiphen > (+)pentazocine, and significantly correlated with potency at sigma 2 binding sites in guinea pig brain (r = 0.90, p < 0.01). The immunomodulatory activities of the sigma ligands 1,3-di(2-tolyl)guanidine, haloperidol. (-)pentazocine and (+)pentazocine on CD3-induced proliferation, IL-2 production and Ca2+ flux in human lymphocytes did not reveal any consistent pharmacology that could be ascribed to potency of these compounds at sigma binding sites. Collectively the data demonstrate that the [3H]1,3-di(2-tolyl)guanidine binding site on Jurkat cell membranes has a pharmacology consistent with sigma receptors, but no modulation of functional activity or intracellular events in human peripheral blood lymphocytes correlating with sigma receptors was found.
在从Jurkat T细胞系制备的膜中研究了σ配体[3H]1,3 - 二（2 - 甲苯基）胍（DTG）的结合特性。结合具有饱和性，KD为56±3 nM，Bmax为11706±3173 fmol/mg蛋白质（n = 3）。在Jurkat细胞系中，σ参考化合物抑制结合的效力顺序为：艾芬地尔> 1,3 - 二（2 - 甲苯基）胍>氟哌啶醇>卡比沙明>（+）3 - （3 - 羟苯基） - N - 丙基哌啶（（+）3 - PPP）>（ - ）喷他佐辛>卡拉美芬>（+）喷他佐辛，并且与豚鼠脑σ2结合位点的效力显著相关（r = 0.90，p <0.01）。σ配体1,3 - 二（2 - 甲苯基）胍、氟哌啶醇、（ - ）喷他佐辛和（+）喷他佐辛对人淋巴细胞中CD3诱导的增殖、IL - 2产生和Ca2 +通量的免疫调节活性未显示出任何可归因于这些化合物在σ结合位点效力的一致药理学特性。总体而言，数据表明Jurkat细胞膜上的[3H]1,3 - 二（2 - 甲苯基）胍结合位点具有与σ受体一致的药理学特性，但未发现人外周血淋巴细胞中与σ受体相关的功能活性或细胞内事件的调节作用。
