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Stimulation of proximal small intestinal mucosal growth by luminal polyamines
J Y Wang1, S A McCormack, M J Viar
1Department of Physiology and Biophysics, University of Tennessee College of Medicine, Memphis 38163.
Abstract:
The purpose of this study was to determine whether luminal polyamines stimulate intestinal mucosal growth in vivo. Rats received 2% alpha-difluoromethylornithine (DFMO) added to their drinking water throughout the experiment. The polyamines spermidine and spermine (3 mg each/100 g body wt) were given intragastrically in combined doses once at 9:30 A.M. and again at 5:30 P.M. Duodenal and jejunal mucosal ornithine decarboxylase (ODC) activity in the DFMO-treated rats was inhibited significantly for the duration of the study. DFMO also markedly decreased the rate of [3H]thymidine incorporation into DNA of duodenal and jejunal mucosa. The decrease in [3H]thymidine incorporation was significant 4 days and maximal 6 and 8 days after beginning treatment with DFMO. Decreased ODC activity and DNA synthesis were paralleled by decreases in total mucosal DNA, RNA, and protein content. Administration of the polyamines significantly reversed the effects of DFMO except the inhibition of ODC. In fact, there were no significant differences in mucosal growth parameters between the controls (without DFMO) and those treated with DFMO plus polyamines. Oral administration of spermidine and spermine at a dose of 4.5 mg each/100 g body wt for 6 days to rats not treated with DFMO increased the normal rate of mucosal growth in the duodenum and jejunum as well. Polyamine accumulation in IEC-6 cells was measured to determine whether it was altered by DFMO. IEC-6 cells took up [3H]putrescine and [3H]spermidine from their surrounding environment and the uptake was stimulated by serum. DFMO (5 mM) totally inhibited the increase in ODC activity but had no effect on the cellular uptake of polyamines in the presence of putrescine.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Luminal polyamines, spermidine and spermine, stimulate intestinal mucosal growth in rats. Inhibiting ornithine decarboxylase (ODC) with DFMO reduced growth, but polyamine administration reversed these effects, except for ODC inhibition.
Area of Science:
- Gastroenterology
- Molecular Biology
- Cell Biology
Background:
- Polyamines are essential for cell growth and proliferation.
- Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis.
- Intestinal mucosal growth is a dynamic process influenced by various factors.
Purpose of the Study:
- To investigate the role of luminal polyamines in stimulating intestinal mucosal growth in vivo.
- To determine if polyamine administration can counteract the growth-inhibitory effects of ODC inhibition.
Main Methods:
- Rats were treated with alpha-difluoromethylornithine (DFMO) to inhibit ODC activity.
- Polyamines (spermidine and spermine) were administered intragastrically.
- Duodenal and jejunal mucosal ornithine decarboxylase (ODC) activity, [3H]thymidine incorporation, and mucosal DNA, RNA, and protein content were measured.
- Polyamine uptake in IEC-6 cells was assessed in the presence and absence of DFMO.
Main Results:
- DFMO significantly inhibited ODC activity and decreased DNA synthesis, mucosal DNA, RNA, and protein content.
- Polyamines reversed the DFMO-induced decreases in mucosal growth parameters, except for ODC inhibition.
- Exogenous polyamine administration to non-DFMO-treated rats increased normal mucosal growth.
- DFMO inhibited ODC activity in IEC-6 cells but did not affect polyamine uptake.
Conclusions:
- Luminal polyamines play a significant role in stimulating intestinal mucosal growth.
- Polyamines can counteract the negative effects of ODC inhibition on intestinal mucosal growth.
- Targeting polyamine metabolism may offer therapeutic strategies for modulating intestinal growth.