Delta Opioid Receptor and Its Peptide: A Receptor-Ligand Neuroprotection

Meaghan Staples,Cesar Borlongan,Naoki Tajiri,Yuji Kaneko,Sandra Acosta,Mibel Pabon

doi:10.3390/ijms140917410

Meaghan Staples, Cesar Borlongan + Show 4 more

Open Access

https://doi.org/10.3390/ijms140917410

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Abstract

In pursuit of neurological therapies, the opioid system, specifically delta opioid receptors and delta opioid peptides, demonstrates promising therapeutic potential for stroke, Parkinson’s disease, and other degenerative neurological conditions. Recent studies offer strong evidence in support of the therapeutic use of delta opioid receptors, and provide insights into the underlying mechanisms of action. Delta opioid receptors have been shown to confer protective effects by mediating ionic homeostasis and activating endogenous neuroprotective pathways. Additionally, delta opioid agonists such as (D-Ala 2, D-Leu 5) enkephalin (DADLE) have been shown to decrease apoptosis and promote neuronal survival. In its entirety, the delta opioid system represents a promising target for neural therapies.

Highlights

The opioid system is composed of various opioid peptides and their corresponding receptors.Opioids are a group of inhibitory neurotransmitters that are involved in a variety of functions including pain regulation and respiratory rate control
These data suggest that the opioid system is involved in neuroprotection against hypoxic and ischemic events, and is likely mediated primarily by DOR and delta opioid peptides
oxygen-glucose deprivation (OGD)-induced p38 phosphorylation, but no appreciable effect on phosphorylation of JNK, further highlighting that DOR-DADLE neuroprotection may be due to the dynamic balance between the activation of ERK and the p38 [40]

Summary

Introduction

The opioid system is composed of various opioid peptides and their corresponding receptors. Opioid receptors elicit diverse pharmacologic effects depending on their opioid classification. These receptors are present throughout the central and peripheral nervous systems, as well as various peripheral organs including the heart, lungs, liver, and gastrointestinal tract [1,2,3,4,5,6]. It was shown that opioid-induced protection could be inhibited by DOR antagonists, but not MOR and KOR antagonists [10]. These data suggest that the opioid system is involved in neuroprotection against hypoxic and ischemic events, and is likely mediated primarily by DOR and delta opioid peptides

DOR: The Receptor and Neuroprotection

DADLE: The Ligand and Neuroprotection

Conclusions and Future Directions