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Low-dose naltrexone (LDN): Tricking the body to heal itself
Date:9/2/2011

erface and elicit a robust functional response: inhibition of cell proliferation. The question that now can be addressed is which endogenous opioid(s) and opioid receptor(s) are responsible for LDN's effects on cell proliferative processes.

The present study was structured to focus on the relationship of endogenous opioid pathways and the repercussions of intermittent opioid receptor blockade with regard to cell proliferation. A unique tissue culture model of LDN using a short-term exposure to NTX was developed, thereby avoiding the confounding variables introduced by systemic influences and allowing a dissection of the biological events involved. Screening of a wide variety of opioids (some selective for specific opioid receptors) revealed that only exogenous OGF had a profound effect on depressing cell proliferation. Removal of endogenous OGF by antibody neutralization in cultures given a short-term opioid receptor blockade by NTX eliminated the repressive effects of this peptide on cell proliferation, indicating that the repercussions of short-term NTX exposure in vitro was dependent on OGF. Short-term NTX blockade continued to exert a negative effect on cell proliferation even when the classical opioid receptors, μ, δ, and κ, were knocked down by siRNA technology. However, short-term NTX treatment did not repress cell proliferation when cells were subjected to siRNA to the non-classical opioid receptor, OGFr. These results indicate that the effects of short-term NTX in vitro are dependent on the OGF-OGFr axis. Previous studies have shown that the OGF-OGFr axis regulates cell proliferation by altering the G1/S phase of the cell cycle through the cyclin-dependent inhibitory kinases p16 and p21. Knockdown experiments with siRNA show that a short interval of exposure to NTX in tissue culture required p16 and/or p21 in order to have a functional outcome on cellular processes.

The research team was comprised of Dr. Ian S. Zago
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Contact: Dr. Ian Zagon
isz1@psu.edu
717-531-6409
Society for Experimental Biology and Medicine
Source:Eurekalert

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