Biology of the Opioid Growth Factor – Opioid Growth Factor Receptor Axis: Bench to Bedside and Back

Main Article Content

Ian S. Zagon, Ph.D. Patricia J. McLaughlin

Abstract

The Opioid Growth Factor – Opioid Growth Factor Receptor axis was identified nearly 30 years ago in our laboratory when we demonstrated that an endogenous opioid pentapeptide had inhibitory growth activity following injection into normal animals. In addition to validating this action for the peptide, identification, characterization and cloning of the specific receptor related to the opioid growth factor, chemically termed [Met5]-enkephalin, revealed that the receptor was unique in its biochemical and molecular structure, but had pharmacological properties similar to other opioid receptors. Mechanisms associated with binding of the opioid growth factor to its receptor located on the outer nuclear envelop and the transport into the nucleus were identified. The selectively of the peptide for the receptor was demonstrated in normal and cancer cell lines. This uniqueness of the peptide-receptor interaction was evidenced by the duration of receptor blockade in that intermittent blockade resulted in decreased cell replication and complete blockade resulted in accelerated proliferation. Investigations on the mechanism of action, as well as the dysregulation of the Opioid Growth Factor – Opioid Growth Factor Receptor axis in human pathology, have resulted in bench to bedside and bedside to bench discoveries. Receptor blockade by naltrexone has been used clinically for treatment of fatigue and other immune deficiencies in many autoimmune disorders. The research has gone from bench to bedside and has returned to the bench for additional investigation of mechanisms driving the action of the axis and resultant function following receptor blockade.

Keywords: [Met5]-enkephalin, diabetes, dry eye, multiple sclerosis, low-dose naltrexone

Article Details

How to Cite
ZAGON, Ian S.; MCLAUGHLIN, Patricia J.. Biology of the Opioid Growth Factor – Opioid Growth Factor Receptor Axis: Bench to Bedside and Back. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5369>. Date accessed: 22 july 2024. doi: https://doi.org/10.18103/mra.v12i6.5369.
Section
Research Articles

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