Opioid growth factor is present in human and mouse gastrointestinal
tract and negatively regulates dna synthesis.
Zagon, Ian S., Yan Wu, Patricia J. McLaughlin.
Department of Neuroscience and Anatomy, The Pennsylvania State
University, College of Medicine, Hershey, Pennsylvania 17033
APStracts 3:0415R, 1996.
Native opioid peptides serve as growth factors in a number of normal
and neoplastic cells and tissues. This study investigated the
influence of opioids on circadian rhythm-dependent DNA synthesis in
mouse esophagus during homeostatic renewal. In contrast to a labeling
index (LI) of approximately 24.0% at 0630 hours and 5.5% 1600 hours,
disruption of opioid-receptor interaction by the potent opioid
antagonist naltrexone (NTX) (10 mg/kg) in mice resulted in an
elevation of 49% in DNA synthesis of esophageal epithelial cells at
1600 hours but had no effect at 0630 hours. Mice subjected to [Met5]
-enkephalin (1 mg/kg) had a LI that was decreased 23% from control
levels at 0630 hours but was unaffected at 1600 hours. This decrease
in DNA synthesis was blocked by concomitant administration of
naloxone (10 mg/kg); naloxone alone had no influence on cell
replicative processes. In tissue culture studies, NTX and OGF
markedly increased and decreased, respectively, the LI from control
values. Both OGF and its receptor, _, were detected in all but the
cornified layer of mouse esophageal epithelium, and in the epithelial
cells of the stomach and small and large intestines. In addition,
both peptide and receptor were observed in the basal and suprabasal
cells of human esophageal epithelium. These results indicate that an
endogenous opioid peptide (OGF) and its receptor (_) reside in
gastrointestinal epithelium and play a role in cellular renewal
processes in a tonically inhibitory, direct, and circadian rhythm
-dependent fashion.
Received 8 August 1996; accepted in final form 13 November 1996.
APS Manuscript Number R465-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996