Delta opioid agonists inhibit proliferation of highly purified murine CD4+ and CD8+ T-cells

N. A. Shahabi, Burt Sharp

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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-ε; 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 10-1 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. In summary, the dose-response profiles for the anti-proliferative effects of DAME and deltorphin are similar in CD1 and C57BL/6 mice, whereas the profiles are distinctively different for DPDP-E. The effects of DPDP-E appear to be mediated through a δ-like opiate receptor.

Original languageEnglish (US)
Pages (from-to)29-36
Number of pages8
JournalAdvances in Experimental Medicine and Biology
Volume373
StatePublished - Jan 1 1995

Fingerprint

T-cells
Opioid Analgesics
T-Lymphocytes
delta Opioid Receptor
Enkephalins
Thymidine
naltrindole
Opioid Peptides
Inbred C57BL Mouse
Narcotic Antagonists
Serum-Free Culture Media
Opioid Receptors
T-Cell Antigen Receptor
Fluorescence
Experiments
Met-enkephalinamide
N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Delta opioid agonists inhibit proliferation of highly purified murine CD4+ and CD8+ T-cells. / Shahabi, N. A.; Sharp, Burt.

In: Advances in Experimental Medicine and Biology, Vol. 373, 01.01.1995, p. 29-36.

Research output: Contribution to journalArticle

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abstract = "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-ε; 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 10-1 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. In summary, the dose-response profiles for the anti-proliferative effects of DAME and deltorphin are similar in CD1 and C57BL/6 mice, whereas the profiles are distinctively different for DPDP-E. The effects of DPDP-E appear to be mediated through a δ-like opiate receptor.",
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