title: Effect of entacapone on colon motility and ion transport in a rat model of Parkinson's disease.
abstract: OBJECTIVE
  To study the effects of entacapone, a catechol-O-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease (PD) rats.
  
  
  METHODS
  Distribution and expression of catechol-O-methyltransferase (COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitro by means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current (ISC ) technique and scanning ion-selective electrode technique (SIET). Intracellular detection of cAMP and cGMP was accomplished by radioimmunoassay testing.
  
  
  RESULTS
  COMT was expressed in the colons of both normal and PD rats, mainly on the apical membranes of villi and crypts in the colon. Compared to normal controls, PD rats expressed less COMT. The COMT inhibitor entacapone inhibited contraction of the PD rat longitudinal muscle in a dose-dependent manner. The β2 adrenoceptor antagonist ICI-118,551 blocked this inhibitory effect by approximately 67% (P < 0.01). Entacapone increased mucosal ISC in the colon of rats with PD. This induction was significantly inhibited by apical application of Cl(-) channel blocker diphenylamine-2, 2'-dicarboxylic acid, basolateral application of Na(+)-K(+)-2Cl(-)co-transporter antagonist bumetanide, elimination of Cl(-) from the extracellular fluid, as well as pretreatment using adenylate cyclase inhibitor MDL12330A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacapone-induced ISC by 45% (P < 0.01). When SIET was applied to measure Cl(-) flux changes, this provided similar results. Entacapone significantly increased intracellular cAMP content in the colonic mucosa, which was greatly inhibited by indomethacin.
  
  
  CONCLUSIONS
  COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacapone-induced inhibition of colon motility. Entacapone induces cAMP-dependent Cl(-) secretion in the PD rat.
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Li
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Chen-Zhe
authors.initials: CZ
authors.lastname: Liu
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Jing-Dong
authors.initials: JD
authors.lastname: Xu
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Zheng
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Feng
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Li-Sheng Li, Chen-Zhe Liu, Jing-Dong Xu, Li-Fei Zheng, Xiao-Yan Feng, Yue Zhang, Jin-Xia Zhu, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
authors.forename: Jin-Xia
authors.initials: JX
authors.lastname: Zhu
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D065098:Catechol O-Methyltransferase Inhibitors / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D017136:Ion Transport; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D058672:Adrenergic beta-2 Receptor Antagonists; D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D018118:Chloride Channels; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D009570:Nitriles; C071192:entacapone; D016627:Oxidopamine; D000242:Cyclic AMP; D002394:Catechol O-Methyltransferase
keywords: Catechol-O-methyltransferase; Colon motility; Entacapone; Ion transport; Parkinson disease
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