Delta opioid agonists inhibit proliferation of highlypurified murine CD4+ and CD8+ T-cells.
A substantial body of evidence demonstrates that opiates and opioid peptides modulate immune function. The present study used highly purified murine CD4+ and CD8+ T-cells to determine the effects of delta opioid receptor (DOR) agonists on proliferation. Splenic T-cells, obtained from male or female C57BL/6 or CD1 mice, were separated by a fluorescence activated cell sorter. Cells were stimulated to proliferate in serum free medium by cross-linking the T-cell receptor using plate-coated anti-CD3-epsilon, 3H-thymidine uptake was determined at 48 hours. Previous experiments had shown that deltorphin and [D-Ala2]-met-enkephalinamide (DAME), at concentrations from 10(-11) to 10(-7) M, dose dependently inhibited the proliferation of CD4+ and CD8+ T-cells obtained from female C57BL/6 or CD1 mice. Similarly, the experiments herein demonstrate that proliferation of CD4+ T-cells from female CD1 mice was inhibited by 2,5 DPDP-enkephalin (DPDP-E), in direct relation to dose. In contrast, the anti-proliferative response of cells from C57BL/6 mice demonstrated an inverse relationship to dose. At 10(-11) M, the most effective dose of DPDP-E studied, 3H-thymidine uptake was inhibited by 50%. The selective DOR antagonist, naltrindole (10(-12) M), abolished this. DAME was used to compare the effects of DOR agonists on CD8+ T-cells from both strains of female mice. 3H-Thymidine uptake was dose-dependently inhibited to a similar degree in both strains; 10(-7) M DAME maximally reduced proliferation by 70%. DAME had similar effects on both CD8+ and CD4+ T-cells from male mice, and its inhibitory effect was markedly attenuated after 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Shahabi
N A
NA
Endocrine-Neuroscience Research Laboratory, Minneapolis Medical Research Foundation, Minnesota, USA.
Sharp
B M
BM
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004745:Enkephalins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*
D000700:Analgesics; D015704:CD4 Antigens; D016827:CD8 Antigens; D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D004744:Enkephalin, Methionine; D009271:Naltrexone; C022118:enkephalinamide-Met, Ala(2)-; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole