The biology of the opioid growth factor receptor (OGFr).
Opioid peptides act as growth factors in neural and non-neural cells and tissues, in addition to serving for neurotransmission/neuromodulation in the nervous system. The native opioid growth factor (OGF), [Met(5)]-enkephalin, is a tonic inhibitory peptide that plays a role in cell proliferation and tissue organization during development, cancer, cellular renewal, wound healing, and angiogenesis. OGF action is mediated by a receptor mechanism. Assays with radiolabeled OGF have detected specific and saturable binding, with a one-site model of kinetics. Subcellular fractionation studies show that the receptor for OGF (OGFr) is an integral membrane protein associated with the nucleus. Using antibodies generated to a binding fragment of OGFr, this receptor has been cloned and sequenced in human, rat, and mouse. OGFr is distinguished by containing a series of imperfect repeats. The molecular and protein structure of OGFr have no resemblance to that of classical opioid receptors, and have no significant homologies to known domains or functional motifs with the exception of a bipartite nuclear localization signal. Immunoelectron microscopy and immunocytochemistry investigations, including co-localization studies, have detected OGFr on the outer nuclear envelope where it interfaces with OGF. The peptide-receptor complex associates with karyopherin, translocates through the nuclear pore, and can be observed in the inner nuclear matrix and at the periphery of heterochromatin of the nucleus. Signal transduction for modulation of DNA activity is dependent on the presence of an appropriate confirmation of peptide and receptor. This report reviews the history of OGF-OGFr, examines emerging insights into the mechanisms of action of opioid peptide-receptor interfacing, and discusses the clinical significance of these observations.
Zagon
Ian S
IS
Department of Neuroscience and Anatomy, H-109, The Milton S. Hershey Medical Center, The Pennsylvania State University, College of Medicine, 500 University Drive, Hershey, PA 17033, USA. isz1@psu.edu
Verderame
Michael F
MF
McLaughlin
Patricia J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004744:Enkephalin, Methionine / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; D004744:Enkephalin, Methionine