Further studies on the biological characteristics of an endogenous colon mitosis inhibitor: Comparison with some structurally related peptides |
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Authors: | Øyvind Skraastad Karl L Reichelt |
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Institution: | 1. Institute of Pathology (?S) and Pediatric Research Institute (KLR) Rikshospitalet, N-0027, Oslo 1, Norway
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Abstract: | Previous work indicates that the colonic epithelial cell proliferation in mice is reversibly inhibited by the tripeptide pGlu-His-GlyOH
found in aqueous extracts of the intestine. In the present study we examined the possible tissue specificity of the colon
mitosis inhibitor. The mitotic rate in the small intestine, epidermis and forestomach in mice was registered after a single
i.p. injection of the tripeptide. A significantly reduced rate of cell renewal was found at 18 h in the epidermis whereas
no inhibition was observed in the forestomach or ileal epithelium. To investigate whether the amino acid sequence of the tripeptide
is essential for the inhibitory effect, three structurally related bioactive peptides were tested and compared to the effect
of CMI. CMI showed a bell-shaped dose-response relationship as previously shown, whereas the mitotic rate was not reduced
in the colonie epithelium after treatment with either an epidermal mitosis inhibitory pentapeptide, or the dipeptide pGlu-GlyOH,
or an analogue of luteinizing hormone-releasing hormone. The efficacy of the tripeptide was dependent on the basal rate of
cell renewal in the colonie epithelium. When the tripeptide was given at the circadian nadir of cell proliferation a delayed
reduction of the proliferative activity was observed at 6 h after treatment, whereas treatment when the rate of cell proliferation
was at its circadian zenith gave an immediate mitotic inhibition. |
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Keywords: | Cell proliferation Colon Inhibition Peptides tissue specificity |
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