Mu/delta interactions

The work of Devi and associates [22] provided a potential molecular mechanism for mu-delta interactions and a physical basis to explain biochemical observations of a mu-delta opioid receptor complex [23,24]. Their work and the efforts of others [25] have clearly demonstrated that mu and delta receptors can form heterodimers, leading to synergistic interactions and the generation of novel signaling units. This work, in other words, provides a molecular mechanism to explain how it is possible for three basic types of opioid receptors to form a greater number of pharmacologically defined opioid receptor subtypes. 

D Amato R, Holaday JW. Multiple opiate receptors in endotoxic shock evidence for delta involvement and mu-delta interactions in vivo. Proc Natl Acad Sci USA 1984 81 2898-2901. 

The idea that interactions between mu and delta contribute to behavioral and physiological effects of opioid agonists has been considered for over a decade. Evidence for mu/delta cooperativity has been obtained using molecular, cellular, and behavioral approaches [46-52]. However, models of mu/delta interaction have not yet been considered in detail from a circuit perspective. Thus, given that both mu and delta agonists can produce antinociception following focal application within the RVM, the question arises whether mu and delta actions in this system are coordinated or functionally independent. This issue has been addressed from two perspectives. 

In vitro and in vivo studies conducted in the 1980s and 1990s clearly demonstrated synergistic interactions in vivo between mu and delta receptors that were most simply explained by a mu-delta opioid receptor complex. The failure to clone opioid receptors corresponding to the postulated mu-delta opioid receptor complex, as well as other opioid receptor subtypes defined... 

Ananthan S. Opioid ligands with mixed mu/delta opioid receptor interactions an emerging approach to novel analgesics. AAPS J 2006 8 El 18-25. 

Suzuki S, Chuang LE, Yau P, Doi RH, Chuang RY (2002b) Interactions of opioid and chemokine receptors oligomerization of mu, kappa, and delta with CCR5 on immune cells. Exp Cell Res 280 192-200... 

The mu, kappa, and delta opioid receptors have been found to interact with endogenous peptide ligands that share certain pharmacologic properties with opioid drugs. These peptide ligands are derived from at least three different prohormones located in both... 

The third prohormone from which opioid peptides are derived is pro-opiomelanocortin, which yields a number of nonopioid and opioid peptide products (O Donohue and Dorsa 1982). Of these products, beta-endorphin, an untriakontapeptide isolated from camel pituitary gland by Li and Chung (1976)) is thought to interact primarily with mu and delta receptors. 

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