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Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner
I S Zagon1, Y Wu, P J McLaughlin
1Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033.
Abstract:
In addition to neuromodulation, endogenous opioids also serve as growth factors. To investigate the involvement of the naturally occurring opioid peptide [Met5]enkephalin [termed opioid growth factor (OGF)] in the renewal of epithelium, adult mice were given systemic injections of OGF (1 mg/kg) and examined 2 h later at 0700 or 1700 h. DNA synthesis in the tongue was investigated using [3H]thymidine and autoradiography. OGF depressed DNA synthesis of the basal epithelial cells in the tip, and dorsal and ventral surfaces of the tongue (42-44% of control levels) only at 0700 h. This decrease in DNA synthesis was blocked by concomitant administration of the opioid antagonist naloxone (10 mg/kg); naloxone alone had no influence on cell replicative processes. Both OGF and its receptor, zeta (zeta), were detected in the stratified squamous epithelium of the ventral and dorsal surfaces of the tongue by immunocytochemistry. Photodensitometric measurements of immunocytochemical preparations revealed almost twofold more OGF and zeta-receptor immunoreactivity at 1700 h than at 0700 h. These results indicate that an endogenous opioid peptide and its receptor are present and govern cellular renewal processes in the tongue and regulate DNA synthesis in a circadian rhythm-dependent fashion.
Insights
Opioid growth factor (OGF), an endogenous opioid peptide, regulates epithelial renewal in mouse tongues. OGF inhibits DNA synthesis in a circadian rhythm-dependent manner, with effects blocked by naloxone.
Area of Science:
- Endocrinology
- Cell Biology
- Neuroscience
Background:
- Endogenous opioids, like [Met5]enkephalin (opioid growth factor, OGF), function beyond neuromodulation as growth factors.
- The role of OGF in epithelial renewal processes requires further investigation.
Purpose of the Study:
- To investigate the involvement of OGF in the renewal of tongue epithelium in adult mice.
- To determine if OGF regulates DNA synthesis in a circadian rhythm-dependent manner.
Main Methods:
- Adult mice received systemic injections of OGF (1 mg/kg) or OGF with naloxone (10 mg/kg).
- DNA synthesis was assessed using [3H]thymidine and autoradiography at 0700 and 1700 h.
- Immunocytochemistry and photodensitometry were used to detect OGF and its zeta receptor in tongue epithelium.
Main Results:
- OGF significantly depressed DNA synthesis in tongue basal epithelial cells by 42-44% of control levels, but only at 0700 h.
- The OGF-induced decrease in DNA synthesis was completely blocked by co-administration of the opioid antagonist naloxone.
- Both OGF and its zeta receptor were detected in the stratified squamous epithelium, with higher immunoreactivity observed at 1700 h compared to 0700 h.
Conclusions:
- An endogenous opioid peptide (OGF) and its receptor are present in the tongue epithelium.
- OGF plays a role in governing cellular renewal processes and regulating DNA synthesis in the tongue.
- These regulatory processes are dependent on the circadian rhythm.