1. Distinct domains of IFNalpha mediate immune and analgesic effects respectively.
- Author
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Wang YX, Jiang CL, Lu CL, Song LX, You ZD, Shao XY, Cui RY, and Liu XY
- Subjects
- Amino Acid Substitution genetics, Analgesics antagonists & inhibitors, Analgesics immunology, Animals, Antiviral Agents antagonists & inhibitors, Antiviral Agents immunology, Central Nervous System drug effects, Central Nervous System immunology, Cross Reactions immunology, Enzyme-Linked Immunosorbent Assay, Humans, Immune Sera immunology, Interferon-alpha antagonists & inhibitors, Interferon-alpha chemistry, Interferon-alpha genetics, Male, Mutation genetics, Naloxone pharmacology, Narcotics chemistry, Narcotics immunology, Pain Threshold, Protein Structure, Tertiary, Rats, Rats, Sprague-Dawley, Structure-Activity Relationship, Analgesics chemistry, Analgesics pharmacology, Antiviral Agents chemistry, Antiviral Agents pharmacology, Interferon-alpha immunology, Interferon-alpha pharmacology
- Abstract
Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also an analgesic molecule. The analgesic effect of IFNalpha was mediated by mu opioid receptor. After the 129th Tyr residue of human IFNalpha was mutated to Ser, the antiviral activity almost disappeared, but there still remained a strong analgesic activity that could be blocked by naloxone. These results indicate that there exist distinct domains in the IFNalpha molecule, which mediate immune and analgesic effects respectively, and suggest that there are different receptor mechanisms inducing immune and analgesic effects of IFNalpha. However, although the antiviral activity of IFNalpha decreased to 34.1% of wild type IFNalpha after the 122nd Tyr residue was changed to Ser, the analgesic activity of this mutant was lost completely. There were significant cross reactivities between INFalpha and anti-opioid sera. These studies show strong structural and functional similarities between INFalpha and opioid peptides, and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in tertiary structure.
- Published
- 2000
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