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恩他卡朋促进大鼠cAMP依赖的Cl分泌引起胃肠不适 分析测试百科网...





参考文献:Li LS, et al. Neurogastroenterology and Motility, 2011, 23(7): 657-e277.

Entacaponepromotes cAMP-dependent colonic Cl-secretion in rats 恩他卡朋促进大鼠结肠中cAMP依赖型Cl-分泌

Background Entacapone is a promising drug used widely for the treatment ofParkinson’s disease (PD) as a catechol-O-methyl transferase (COMT) inhibitor.However, entacapone has gastrointestinal side effects.The aim of thisstudy was to investigate the effects of entacapone on the epithelial iontransport in rat distal colon, and explore the underlying mechanism.
Methods Thestudy was performed on freshly isolated colonic mucosa-only, submucosa-only andmucosa–submucosa preparations in rat. The short circuit current (ISC) wasmeasured to determine electrogenic ion transport, and a scanning ion-selectiveelectrode technique (SIET) was used to directly measure Cl- flux across the epithelium. The content of intracellular cAMP was measured with radioimmunoassay (RIA).
Key Results Entacaponeincreased mucosal ISC in the rat distal colon. ISC was inhibited significantlyby apical addition of diphenylamine-2,2’-dicarboxylic acid(DPC), a blocker of the Cl- channel, basolateral applicationof bumetanide, an inhibitor of Na+-K+-2Cl- co-transporter (NKCC), emoval of Cl- from the bathingsolution, and pretreatment with MDL 12330A, an inhibitor of adenylate cyclase.Inhibiting endogenous prostaglandin (PG) synthesis with indomethacin,andeliminating submucosal enteric neural activity with tetrodotoxin(TTX)-inhibited entacapone- evoked ISC increases. Similar results were also obtainedwhen Cl- flux was measured with SIET.Entacaponesignificantly increased intracellular cAMP content, which was greatly inhibitedby either indomethacin or TTX in the tissues containing submucosal plexus, andby only indomethacin in the mucosa-only preparations.
Conclusions Inferences Entacapone stimulates cAMP-dependent Cl- secretionin the rat colon,and this process is regulated by endogenous PG and thesubmucosal enteric nervous system.


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