Dipak
Sarkar, professor in the Department of Animal Sciences at the Rutgers
School of Environmental and Biological Sciences and his research team
have been able to take a new pharmacological approach to activate the
immune cells to prevent cancer growth through stimulation of the opiate
receptors found on immune cells.
This
research, funded by the National Institutes of Health-National
Institute on Alcohol Abuse and Alcoholism, is featured on the cover of
the May 11 issue of the Journal of Biological Chemistry.
It describes two structurally different but functionally similar opioid
receptors, Mu- and Delta-opioid receptors. These receptors form protein
complexes as either two structurally similar receptors as a
homodimer—formed by two identical molecules—or two structurally
dissimilar protein complexes as a heterodimer—formed by ethanol
inducement—in immune cells. The team pharmacologically fooled these two
structurally different but functionally similar opioid receptors to form
more homodimers so that opioid peptide increases the immune cells’
ability to kill tumor cells.
“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,” says Sarkar.
Opioids,
like endorphins, communicate with the immune system, so when there is a
deficit of endorphin—due to fetal alcohol exposure, alcoholism and drug
abuse, anxiety, depression and chronic psychological stress—the body
undergoes stress shocks and, as Sarkar suggests, causes “immune
incompetence.”
“Opioids
act as the regulator of body stress mechanism, so when endorphins are
low, body stress indicators are high,” says Sarkar, who directs the
Endocrine Research Program at Rutgers and is a faculty member of the
Rutgers Center of Alcohol Studies.
“What’s
new about this latest research is that when we combine the Mu receptor
blocker (antagonist) with the Delta receptor stimulator (agonist), the
immune cells accrue increased foreign cell-killing ability,” explains
Sarkar. “This makes the body highly effective in fighting against
bacterial infection and tumor growth.”
Sarkar
believes that combining this opioid antagonist and agonist may have
potential therapeutic value in humans for the treatment of immune
incompetence, cancer, pain and ethanol-dependent diseases.
Previous
research by the Sarkar group showed that replenishing endorphins by
cell therapy did prevent many of the stress and immune problems in fetal
alcohol-exposed test subjects. However, cell therapy is highly complex,
involving the cumbersome process of producing endorphin cells from
neural stem cells of patients and can sometimes result in rejection and
other issues.
The beginning of the team’s interest
into how stress causes diseases started with the observation that
mothers who suffer from alcohol abuse or with other developmental
problems often give birth to children who exhibited hype-stress
responses, linked to childhood disease, child abnormality, immune
diseases and cancer.
As
part of their investigation, the Sarkar research team learned that the
endogenous opioid system in the brain is abnormal in kids and adults who
demonstrate hyper-stress responses.
“With
the link between hyper-stress responses and manifested immune issues,
the goal has been to replenish the opioid deficit in the brain and lead
to an effective therapy for immune and other diseases,” explained
Sarkar.
The
team also found that when people consume alcohol, the effectiveness of
the body’s ability to defend against viral and bacterial invasion, and
fight against cancer decreases.
“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.
They
hope that the promise of their novel pharmacological approach that
modifies the activity of the opioid receptors of immune cells brings
them one step closer in the long road to therapeutic advances.
