TY - JOUR
T1 - The opioid growth factor-opioid growth factor receptor axis
T2 - Homeostatic regulator of cell proliferation and its implications for health and disease
AU - McLaughlin, Patricia J.
AU - Zagon, Ian S.
N1 - Funding Information:
This research was supported by grants from NIH , American Diabetes Association , Philip Morris and National Multiple Sclerosis Society . The authors wish to express much gratitude to the many students, technicians, and collaborators who have contributed to our knowledge of the OGF–OGFr axis.
PY - 2012/9/15
Y1 - 2012/9/15
N2 - The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.
AB - The opioid growth factor (OGF), chemically termed [Met5]- enkephalin, is an endogenous opioid peptide that interacts with the OGF receptor (OGFr) to delay the G1/S interface of the cell cycle by modulating cyclin-dependent inhibitory kinase (CKI) pathways. The OGF-OGFr axis is a tonically active, inhibitory pathway that is an important regulator during homeostasis and re-epithelialization, and plays a role in the onset and progression of autoimmune diseases and cancer. Modulation of the OGF-OGFr axis can be accomplished by a variety of pharmacological and molecular approaches including use of intermittent or continuous exposure to the opioid antagonist naltrexone, genetic manipulation of OGFr expression, and antibody neutralization of OGF. Clinically, OGF is a biological therapy that has potential application for treatment of cancer. Currently, naltrexone at low dosages is being evaluated for treatment of autoimmune diseases such as Crohn's and multiple sclerosis. High dosages of naltrexone are effective in reversing dry eye and accelerating the repair of corneal abrasions in normal and diabetic rats; these studies are under investigation in the clinical setting. Naltrexone also enhances full-thickness wound closure in animal models of Type 1 or Type 2 diabetes, and translation of this knowledge to the clinic is planned. In summary, understanding the OGF-OGFr axis as a homeostatic regulator of proliferation has substantial implications for maintaining human health and treatment of disease.
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U2 - 10.1016/j.bcp.2012.05.018
DO - 10.1016/j.bcp.2012.05.018
M3 - Comment/debate
C2 - 22687282
AN - SCOPUS:84864953326
SN - 0006-2952
VL - 84
SP - 746
EP - 755
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 6
ER -
