Molecular Characterization of Opioid Receptors

Abstract

Though opioid receptors are more difficult to purify and characterize than other cell surface receptors, significant progress has been made in the past several years. At least a dozen groups have now reported purification of opioid-binding proteins, either in a form that retains ligand-binding properties, or in a covalently bound form. Although there are some discrepancies in the molecular weights of these proteins, it is significant that many investigators have reported a molecular weight of about 60 kd for the receptor, regardless of whether it is of the mu, delta, or kappa type. This finding, together with immunological evidence, suggests that different opioid receptor types may be highly similar, and could conceivably even share a common ligand-binding subunit. Several groups have prepared monoclonal or polyclonal antibodies to purified opioid-binding proteins, which should be useful in mapping the brain regional distribution of the opioid receptors, determining the regions in the peptide involved in ligand binding and association with second messengers, and in determining the relationships among different opioid receptor types. One group has in fact already established an antigenic similarity between a mu-selective opioid-binding protein in mammalian brain, and the delta opioid receptor in NG108-15 neuroblastoma-glioma hybrid cells. One group has reported cloning of the cDNA for a purified opioid-binding protein. Somewhat surprisingly, its predicted amino acid sequence places it in the immunoglobulin superfamily, with strongest homologies to cell-adhesion molecules such as N-CAM. MAG, amalgam and fasciclin II, as well as receptors for peptides such as PDGF and interleukin-6. However, this is consistent with evidence that opioids can modulate cell-cell interactions of monocytes, and provides further support for links between opioids and the immune system. The second messengers mediating opioid actions are still unknown. Opioid agonists affect the activity of adenylate cyclase and ion channels in some tissues, but neither has been shown to mediate opioid analgesia. The sequence homologies of the purified opioid-binding protein OBCAM with tyrosine kinase growth factor receptors suggest additional possibilities for second messengers.

Upregulation of Galanin Binding Sites and GalR1 mRNA Levels in the Mouse Locus Coeruleus Following Chronic Morphine Treatments and Precipitated Morphine Withdrawal

“…In the current study, we show that galanin receptor levels do not change significantly during chronic morphine treatment alone. Previous studies have shown that opioid receptor levels are also unchanged by this treatment (Loh and Smith 1990). In contrast, 5 h following naltrexone-precipitated withdrawal, galanin receptor binding increased by approximately 150%, and GalR1 mRNA levels increased approximately 120%.…”

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

“…Galanin, opioid, and DA receptors are GPCRs that modulate many signaling pathways including those involving ERK1/2 (Belcheva et al, 2005(Belcheva et al, , 2001Hawes et al, 2006a;Loh and Smith, 1990;Williams et al, 2001). Chronic morphine exposure (Berhow et al, 1996) and stimulation of several GPCRs, including opioid receptors, leads to ERK activation in the VTA (Eitan et al, 2003) and inhibition of ERK activity in the VTA suppresses the rewarding effects of morphine (Ozaki et al, 2004).…”

Morphine Negatively Regulates Interferon-γ Promoter Activity in Activated Murine T Cells through Two Distinct Cyclic AMP-dependent Pathways

“…In neuronal cells, morphine binds to a G protein-coupled -opioid receptor to induce analgesia (9,10). Activation of the -opioid receptor leads to regulation of several intracellular effectors, such as modulation of adenylyl cyclase activity (11).…”