AIM: To study the effects of entacapone, a catecholO-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease(PD) rats.METHODS: Distribution and expression of catecholO-methy...AIM: To study the effects of entacapone, a catecholO-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease(PD) rats.METHODS: Distribution and expression of catecholO-methyltransferase(COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitroby means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current(I SC) technique and scanning ion-selective electrode technique(SIET). Intracellular detection of c AMP and c GMP 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 MDL12330 A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacaponeinduced ISC by 45%(P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular c AMP content in the colonic mucosa, which was greatly inhibited by indomethacin.CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacaponeinduced inhibition of colon motility. Entacapone induces c AMP-dependent Cl- secretion in the PD rat.展开更多
基金Supported by National Natural Science Foundation of China,No.81270443,No.81274173 and No.31300954
文摘AIM: To study the effects of entacapone, a catecholO-methyltransferase inhibitor, on colon motility and electrolyte transport in Parkinson's disease(PD) rats.METHODS: Distribution and expression of catecholO-methyltransferase(COMT) were measured by immunohistochemistry and Western blotting methods. The colonic smooth muscle motility was examined in vitroby means of a muscle motility recording device. The mucosal electrolyte transport of PD rats was examined by using a short-circuit current(I SC) technique and scanning ion-selective electrode technique(SIET). Intracellular detection of c AMP and c GMP 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 MDL12330 A. As an inhibitor of prostaglandin synthetase, indomethacin can inhibit entacaponeinduced ISC by 45%(P < 0.01). When SIET was applied to measure Cl- flux changes, this provided similar results. Entacapone significantly increased intracellular c AMP content in the colonic mucosa, which was greatly inhibited by indomethacin.CONCLUSION: COMT expression exists in rat colons. The β2 adrenoceptor is involved in the entacaponeinduced inhibition of colon motility. Entacapone induces c AMP-dependent Cl- secretion in the PD rat.
