ABSTRACT
From the initial hypothesis of Martin et al. [1] on the existence of multiple opioid receptors and the discovery of the endogenous opioid peptides [2-4], numerous studies have reported on the signaling and cellular control of these opioid receptors. In most instances, the molecular mechanism studies have been hampered by the presence of heterogeneous receptor or cell populations. The delta opioid receptor, with its expression in homogeneous clonal cell lines such as neuroblastoma x glioma NG108-15 hybrid cells [5] or in neuroblastoma N4TG2 [6], has been the best studied among the opioid receptors. With the reported cloning of the delta opioid receptor by Evans and Kieffer and their coworkers [7,8], followed by the cloning of mu and kappa opioid receptors [9-14], further understanding of the molecular mechanism of opioid receptor function was obtained by the heterologous expression of these cloned receptors in various systems and the subsequent receptor mutagenesis studies. The importance of the delta opioid receptor activity was demonstrated by absence of morphine tolerance in the delta opioid receptor null mice [15]. Thus, it is critical that the basis of the delta opioid receptor signaling
and the cellular control of such signaling are fully understood. There are numerous review articles and also several chapters within this book that discuss the cloning and the structure-activity studies of the delta opioid receptor. In this chapter, we will review briefly the studies on the delta opioid receptor signal transduction processes, and the subsequent cellular regulation of the receptor activities.
