June 7th, 2012 by Michael Ricciardi
A Rutgers University molecular biology team led by Dr. Dipak Sarkar has developed a promising new technique for marshaling immune cell response to diseased tissue. The technique being developed — based upon stimulating immune cell opiate receptors — offers a potent treatment option against immune disease and cancer.
In preliminary research reported in the May 11 issue of the Journal of Biological Chemistry, the team used a “new pharmacological approach” to trigger immune cells activity… “leading to efficient tumor cell clearance.”
Almost every immune cell in the human body has opioid receptors embedded in its surface membrane. The body’s endogenous opioids — such as endorphins and enkephalins — are used by these cells to communicate with the rest of the immune system so as to ensure a coordinated and efficient attack on any “foreign” (infected, or cancerous) cell. But when our bodies become stressed from disease, injury, alcohol or drug abuse, or due to mental depression and anxiety, they develop a shortage of these opioids, leading to a condition termed “immune incompetence”.
“Opioids act as the regulator of body stress mechanism, so when endorphins are low, body stress indicators are high,” stated Sarkar in a press release.
So then, given the importance of these proteins, if one were to find a way to stimulate the formation of protein receptors on immune cell surfaces, then in theory this should stimulate the immune system to act, that is, produce more natural killer (NK) T cells.
That is what the team set out to do. The key lay in recognizing the two types of molecular structures — the protein complexes — that these opioid receptors can form.
Two Receptors — Mu and Delta — Different but Similar
The two main types of opioid receptors are termed Mu (MOR) and Delta (DOR) and while they are not built the same they have similar functions and act together in a feedback type system. The receptors also form into protein complexes of two types: structurally similar homodimers (formed by two identical molecules) and heterodimers (formed from two dissimilar molecules), with the latter type formed by ethanol (alcohol) inducement.
The tricky thing here is that one type of dimer — the homodimer — is more conducive to opioid (receptor) binding (the other is not and leads to oxic effects’). Using the new pharmacological technique, the team was able to “fool” the Mu and Delta receptors to form more homodimers than heterodimers, so as to reverse the opioid deficit and increase the cell’s ability to attack tumor cells.
As impressive as the new technique is, the most novel finding from this research is that when the Mu receptor “blocker” (known as an antagonist) and the Delta receptor “stimulator” (an agonist) were combined, this allowed immune cells to “accrue increased foreign cell-killing ability.” The super ability makes the body highly effective at combating disease, whether a bacterial/viral infection or tumor cell.
A Potentially Major Therapeutic Advance
“The potential for this research can lead to production of endogenous opioids in the brain and the periphery becoming more effective in regulating stress and immune function,” stated Sarkar in the same press release.
Dipak Sarkar directs the Endocrine Research Program at Rutgers (Department of Animal Sciences, Rutgers School of Environmental and Biological Sciences) and is a faculty member of the Rutgers Center of Alcohol Studies.
His team also found that the consumption of alcohol lessens the effectiveness of the body’s immune system to defend against disease and fight cancer.
“The overall goal of our research program is to increase our understanding of and develop new therapy for the treatment of cancer, immune and other alcoholism-induced diseases,” says Sarkar.
An excerpt from the paper abstract:
Ethanol treatment increased MOR and DOR heterodimers while it decreased the cellular levels of MOR and DOR monomers and homodimers. The opioid receptor homodimerization was associated with an increased receptor binding, and heterodimerization was associated with a decreased receptor binding and the production of cytotoxic factors. Similarly, in vivo, opioid receptor dimerization, ligand binding of receptors, and cell function in immune cells were promoted by chronic treatment with an opiate antagonist but suppressed by chronic ethanol feeding. Additionally, a combined treatment of an MOR antagonist and a DOR agonist was able to reverse the immune suppressive effect of ethanol and reduce the growth and progression of mammary tumors in rats.
The research paper is entitled: Opiate Antagonist Prevents μ- and δ-Opiate Receptor Dimerization to Facilitate Ability of Agonist to Control Ethanol-altered Natural Killer Cell Functions and Mammary Tumor Growth
Top Photo: (T lymphocyte) Nicolas Grandjean (CC – BY – SA 3.0)
Dipak Sarkar Photo Credit: Rutgers University
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