Enteric circular muscle dysfunction in the cystic fibrosis mouse small intestine.

Enteric circular muscle dysfunction in the cystic fibrosis mouse small intestine.
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DOI:
10.1111/j.1365-2982.2009.01418.x
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发表时间:
2010-03
影响因子:
3.5
通讯作者:
Meldi L
Meldi L
中科院分区:
医学3区
文献类型:
--
作者:
de Lisle RC;Sewell R;Meldi L

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Cystic fibrosis (CF) has multiple effects on the gastrointestinal system, including altered motility. The Cftr knockout mouse model of CF has impaired small intestinal transit but the mechanism is unknown. Behavior of circular smooth muscle was studied in an organ bath. Expression levels of prostaglandin (PG) degradative genes was measured by quantitative RT-PCR, and PGE2 levels were measured by enzyme immunoassay. CF circular muscle activity was erratic and had variable frequency of contractions, as compared to WT. The CF tissue was nonresponsive to cholinergic stimulation or direct KCl depolarization. PGE2 and PGF2α are significantly elevated in the CF mouse small intestine, and we hypothesized these contribute to impaired smooth muscle activity. After inhibition of PG synthesis, the CF circular muscle exhibited greater cholinergic responsiveness, which was reversed by exogenous PGE2. PGF2α enhanced activity of CF tissue only after inhibition of PG synthesis. The enteric microbiota was implicated in PGE2 mediated dysmotility because broad spectrum antibiotic treated WT mice, which have slowed transit, exhibit impaired circular muscle activity. This was accompanied by decreased expression of PG degradative genes and increased intestinal PGE2 levels. Furthermore, administration of oral laxative, which eradicates bacterial overgrowth and improves transit in CF mice, increased expression of PG degradative genes, decreased PGE2 levels, and improved CF muscle activity. These results suggest that the enteric microbiota modulates PGE2 levels in a complex manner, which affects enteric smooth muscle activity and contributes to slower small intestinal transit in CF.
DOI: 10.1111/j.1476-5381.1981.tb09989.x
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