Analgesic effect of interferon-alpha via mu opioid receptor in the rat.
Using the tail-flick induced by electro-stimulation as a pain marker, it was found that pain threshold (PT) was significantly increased after injecting interferon-alpha (IFN alpha) into the lateral ventricle of rats. This effect was dosage-dependent and abolished by monoclonal antibody (McAb) to IFN alpha. Naloxone could inhibit the analgesic effect of IFN alpha, suggesting that the analgesic effect of IFN alpha be related to the opioid receptors. Beta-funaltrexamine (beta-FNA), the mu specific receptor antagonist could completely block the analgesic effect of IFN alpha. The selective delta-opioid receptor antagonist, ICI174,864 and the kappa-opioid receptor antagonist, nor-BNI both failed to prevent the analgesic effect of IFN alpha. IFN alpha could significantly inhibit the production of the cAMP stimulated by forskolin in SK-N-SH cells expressing the mu-opioid receptor, not in NG108-15 cells expressing the delta-opioid receptor uniformly. The results obtained provide further evidence for opioid activity of IFN alpha and suggest that this effect is mediated by central opioid receptors of the mu subtype. The evidence is consistent with the hypothesis that multiple actions of cytokines, such as immunoregulatory and neuroregulatory effects, might be mediated by distinct domains of cytokines interacting with different receptors.
Jiang
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Department of Neurobiology, Second Military Medical University, Shanghai, People's Republic of China. jiangclk@online.sh.cn
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D000698:Analgesia; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007276:Injections, Intraventricular; D007370:Interferon Type I / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000502:physiology*; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D007370:Interferon Type I; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D011994:Recombinant Proteins; D009270:Naloxone; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine