[3H]1,3-di(2-tolyl) guanidine binds to a sigma 2 receptor on Jurkat cell membranes, but sigma compounds fail to influence immunomodulatory events in human peripheral blood lymphocytes.
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.
Department of Biochemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426, USA.
D L
DL
DeHaven-Hudkins
J D
JD
Daubert
D G
DG
Sawutz
L
L
Tiberio
Y
Y
Baine
D001667:Binding, Competitive / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology; D006146:Guanidines / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D017480:Receptors, sigma / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D006146:Guanidines; D007376:Interleukin-2; D009294:Narcotics; D017480:Receptors, sigma; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine