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Published on: January 26, 2016
Opioid antagonist modulation of DNA synthesis in mouse tongue epithelium is circadian dependent
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 possible involvement of opioid peptides in the renewal of epithelium, mice were given systemic injections of the opioid antagonist, naltrexone (NTX) (10 mg/kg). Disruption of opioid-receptor interaction by NTX resulted in an elevation (43-150% from control levels) of the number of basal epithelial cells undergoing DNA synthesis in the tip, dorsal, and ventral surfaces of the tongue. This stimulatory effect lasted up to 8 h following drug exposure, and was recorded at 1700 h but not 0700 h. These results are the first indication that endogenous opioids function in cellular renewal processes, and do so in a circadian rhythm-dependent manner.
Insights
Endogenous opioids act as growth factors. Blocking opioid receptors with naltrexone (NTX) stimulated epithelial cell renewal in mouse tongues, indicating a role in circadian-dependent cellular renewal.
Area of Science:
- Cell Biology
- Endocrinology
- Physiology
Background:
- Endogenous opioids are known for neuromodulation.
- Emerging evidence suggests opioid peptides may also function as growth factors.
- Their role in epithelial renewal remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of opioid peptides in epithelial renewal.
- To determine if disrupting opioid-receptor interactions affects cell proliferation.
Main Methods:
- Systemic injections of naltrexone (NTX), an opioid antagonist, were administered to mice.
- The number of basal epithelial cells undergoing DNA synthesis was quantified.
- Experiments were conducted at different times of day (0700 h and 1700 h).
Main Results:
- Naltrexone administration significantly increased DNA synthesis in tongue epithelial cells (43-150% above control).
- This stimulatory effect was observed on the tip, dorsal, and ventral tongue surfaces.
- The effect was transient, lasting up to 8 hours post-injection, and showed circadian rhythm dependency (present at 1700 h, absent at 0700 h).
Conclusions:
- This study provides the first evidence that endogenous opioids regulate cellular renewal processes.
- Opioid peptide involvement in epithelial renewal is dependent on the circadian rhythm.
- Targeting opioid pathways may offer novel strategies for promoting tissue regeneration.
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