Abstract
We investigated the effects of (+)-4-[(α R)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80), a nonpeptidic delta-opioid receptor-selective agonist, on rat leukocyte functions. Intracerebroventricular injection of SNC 80 (20 nmol) in Fischer 344N male rats did not affect splenic natural killer cell activity compared with intracerebroventricular saline-injected controls. SNC 80 also had no effect on concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic and thymic lymphocyte proliferation in most experiments. In some experiments, however, SNC 80 significantly (P < .01) caused a 41 to 93% increase of concanavalin A-, anti-T cell receptor-, interleukin-2- and anti-T cell receptor + interleukin-2-induced splenic lymphocyte proliferation compared to controls. Additionally, SNC 80 did not significantly affect splenic T cell or natural killer cell populations as measured by the expression of T cell receptorαβ, and T helper (CD4), T suppressor/cytotoxic (CD8) and natural killer cell surface markers. Finally, SNC 80 did not affect interferon-γ- or lipopolysaccharide (LPS)-induced splenic nitric oxide, and LPS-induced tumor necrosis factor-α production by splenic macrophages. These results suggest that SNC 80 could be useful in the treatment of pain without suppressing immune function. However, the potential immunoenhancing properties of SNC 80 may be also valuable in immunocompromised individuals.
Footnotes
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Send reprint requests to: Dr. Richard J. Weber, Section of Medical Sciences, Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria, Box 1649, Peoria, IL 61656-1649.
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↵1 This work was supported by National Institutes of Health R01 Grant DA/AI08988. Animals used in these studies were maintained in accordance within the Guide for the Care and Use of Laboratory Animals.
- Abbreviations:
- SNC 80
- (+)-4-[(α R)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide
- Con A
- concanavalin A
- FACS
- fluorescent antibody cell sorter analysis
- FITC
- flourescein isothiocyanate
- HPLC
- high-performance liquid chromatography
- IL-2
- interleukin-2
- ICV
- intracerebroventricular
- NK
- natural killer
- antiTCR
- IgG1 monoclonal antibody to rat T cell receptorαβ
- CD4
- IgG1 monoclonal antibody to rat T helper cells
- CD8
- IgG1 monoclonal antibody to rat T suppressor/cytotoxic cells
- NKCR
- IgG1kmonoclonal antibody to rat NK cells
- LPS
- lipopolysaccharide
- DPDPE
- d-Pen2,d-Pen5-enkephalin
- DAMGO
- H-Tyr-d-Ala-Gly-Phe(N-Me)-Gly-ol
- Received October 3, 1997.
- Accepted March 24, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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