Immunoregulatory properties of (+)-pentazocine and sigma ligands.
(+)-Pentazocine, phencyclidine, and other sigma ligands including 1,3-di-(o)-tolylguanidine (DTG), (+)-1-propyl-3-(3-hydroxyphenyl) piperidine [(+)-PPP] and haloperidol were investigated for their potential immunoregulatory properties. High concentrations (10(-5) M) of DTG and haloperidol were found to suppress in vitro murine splenocyte natural killer activity while equivalent concentrations of (+)-pentazocine, (-)-pentazocine and (+)-PPP were without effect. In a reciprocal fashion, lower doses (10(-9) M) of DTG enhanced natural killer activity. Sigma ligands were also found to affect in vitro polyclonal immunoglobulin production following mitogen stimulation. Specifically, high concentrations (10(-6) M) of haloperidol significantly (P < 0.001) suppressed pokeweed mitogen (PWM)-stimulated IgG and IgM production, yet enhanced lipopolysaccharide (LPS)-stimulated IgM production by murine splenocytes. Lower concentrations (10(-8) to 10(-10) M) enhanced (two- to fourfold) PWM-induced IgM production and LPS-stimulated IgG and IgM production. At high concentrations (10(-6)), (+)-pentazocine suppressed (P < 0.01) LPS-induced polyclonal IgG and IgM but enhanced (P < 0.01) PWM-induced IgM production. Both DTG and (-)-pentazocine (10(-8) to 10(-10) M) significantly augmented (two- to threefold) LPS-stimulated murine splenocyte production of polyclonal IgM. Intracellularly, (-)-pentazocine (10(-9) M), haloperidol (10(-7) M), DTG (10(-7) M) and (+)-PPP (10(-5) to 10(-9) M) enhanced forskolin (10(-6) M)-induced cAMP production in splenic lymphocytes while (+)-pentazocine was without effect. Collectively, the data suggest functional and biologically relevant sigma receptors on cells of the immune system.
Carr
D J
DJ
Department of Microbiology, Immunology and Parasitology, Louisiana State University Medical Center, New Orleans 70112-1393.
Mayo
S
S
Woolley
T W
TW
DeCosta
B R
BR
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007108:Immune Tolerance / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010423:Pentazocine / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000276:immunology; D017480:Receptors, sigma / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D006146:Guanidines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011043:Pokeweed Mitogens; D017480:Receptors, sigma; C050232:1,3-ditolylguanidine; D010423:Pentazocine