[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.
DeHaven-Hudkins
D L
DL
Department of Biochemistry, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, PA 19426, USA.
Daubert
J D
JD
Sawutz
D G
DG
Tiberio
L
L
Baine
Y
Y
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