Recombinant μ‐δ Receptor as a Marker of Opiate Abuse

Abstract

The brain is particularly vulnerable to drugs of abuse changing the neuroreceptor functions. Opiates interact and overstimulate heterogeneous opioid receptors leading to their desensitization, internalization, and activation of recombinant opioid receptor. The molecular properties of rat and human brain recombinant μ‐δ receptor were compared with those of purified μ‐ and δ‐receptors. cDNA coding the unique fragment of recombinant μ‐δ receptor was isolated and sequenced. We hypothesized that recombinant μ‐δ receptor may be a hallmark of opiate abuse. Peptide fragments of the μ‐ (MOR), δ‐ (DOR), and recombinant μ‐δ‐ (MDOR) receptors were used as antigens to assess the presence of autoantibodies in the blood of rats that self‐administered heroin and cocaine, as well as drug abusers. Significant steady elevation of MDOR autoantibodies were measured in sera of rats that self‐administered heroin compared to that for cocaine and vehicle animals. The appearance and increased level of MDOR autoantibodies in opiate abusers correlated with severity of the disorder and duration of drug exposure.

Autoantibodies against opioid or glutamate receptors are associated with changes in morphine reward and physical dependence in mice

“…An elevation of circulating aAbs directed against MDOR and GluR1 receptors was recently demonstrated in human opiate addicts (Dambinova and Izykenova 2002) and in morphine-treated rats (Granstrem et al 2006). Here, we describe specific neurobehavioral alterations associated with an elevation of circulating aAbs in mice immunized with these two selected neuroreceptor fragments.…”

“…It has recently been shown that μ-δ interacting complexes exist and that occupancy of δ receptors is sufficient to enhance μ receptor binding and signaling activity (Gomes et al 2000(Gomes et al , 2004Bailey and Connor 2005). In a previous study, Dambinova and Izykenova (2002) used a recombinant MDOR fragment as antigen to demonstrate the presence of aAbs to MDOR in the blood of rats trained to self-administer heroin as well as in human drug abusers. The same fragment was used as an immunogen in the present study.…”

Role of Opioidergic System in Humoral Immune Response

“…Such observations support the hypothesis that, opiates could be common mediators between the nervous and the immune system. The high levels of aAbs to MDOR were also observed in heroin selfadministering rats as well as in human addicts and shown as a function of severity of opiate addiction (Dambinova and Izykenova, 2002), suggesting that opiate addiction may be somehow associated with autoimmune response/processes. Koziol and collègues (1997) compared the range of ANA in "healthy" individuals in comparison with patients with autoimmune disorders such as systemic lupus erythematosus, systemic sclerosis, sjogren's syndrome and rheumatoid arthritis, or soft tissue rheumatism.…”

Impact of Opioid Use in Hematological Malignancies: Clinical, Immunological and Concomitant Aspects

“…Only a few studies have attempted to determine factors that connect opiate use with the development of autoimmune processes. Several authors have suggested that administration of an opiate agent was associated with elevated levels of autoantibodies to mu delta-opiate receptors (MDORs) in non-drug users as well as in heroin addicts [ 58 , 59 ].…”