Opioid growth factor and the zeta (f) opioid receptor are present and function in mammalian esophagus

The influence of the opioid growth factor (OGF), [Met⁵]-enkephalin, on the generation of epithelial cells in the esophagus of C57/BL6 mice was examined. At 0630 when the labeling index (LI) of basal epithelium (BE) of control animals (CO) was highest (24.0 ±0.6), mice given OGF had reductions of 22.8% 2 hr after injection. At 1600 hr when the LI of the BE of CO was lowest (5.5 ±0.2), OGF had no effect. Blockade of opioid-receptor interaction by injection of the opioid antagonist naltrexone (NTX) increased the LI by 49.1% of CO levels at 1600 hr, but had no effect at 0630 hr. At 0200 hr, an intermediate time selected between the peak and trough of cell proliferation (a control LI of 16.7 ±0.6), OGF decreased the LI by 33.9% and NTX increased the LI by 36.1% from CO values. Imnunocytochemistry using antibodies to the OGF [Met ]-enkephalin, and to the receptor for OGF - zeta (f), revealed intense staining of the cytoplasm of BE and suprabasal cells in mice; cell nuclei appeared to have no immunoreactivity. A similar profile of staining was noted in human esophagus. These results indicate: a) a native opioid functions as a tonic inhibitory growth factor in cellular renewal of the esophagus, b) OGF-regulation of DNA synthesis in the esophagus obeys the principles of circadian rhythm, and c) both the growth peptide and its receptor are present in mouse and human esophagus. Supported by NIH grant NS20500.