Immunomodulation by opioid peptidomimetic compound

Narayan, Prem ; Singh, Vijay K. ; Agarwal, Shyam S. ; Tandon, Ruchi ; Haq, Wahajul ; Raghubir, Ram ; Dhar, Manojit M. (2001) Immunomodulation by opioid peptidomimetic compound NeuroImmunoModulation, 9 (3). pp. 134-140. ISSN 1021-7401

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Objective: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)2-CH2-O-Phe-NH2(1), Tyr-NH-C6H5-(o)-CH2-CH2-O-Phe-NH2 (2), Tyr-NH-CH2-CH2-O-Phe-NH2 (3) and Tyr-NH-CH(D-Et)-CH2-O-Phe-NH2 (4). Methods: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-α (TNF-α ) and nitric oxide. Results: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the μ -opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and β -funaltrexamine hydrochloride (μ -opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-α and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. Conclusion: These observations suggest that compound 3 inhibits MLR through μ -opioid receptor present on cells.

Item Type:Article
Source:Copyright of this article belongs to Karger Publisher.
Keywords:Immunomodulator; Mixed Lymphocyte Reaction; Nitric Oxide; Opioid Peptide
ID Code:51
Deposited On:16 Sep 2010 10:51
Last Modified:11 May 2011 07:48

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