Entacapone promotes cAMP-dependent Cl- secretion in rats and causes gastrointestinal discomfort

Entacapone (Entacapone) is a drug widely used in the treatment of Parkinson's disease (PD) and an inhibitor of catechol-O-methyltransferase (COMT). However, entacapone has gastrointestinal side effects, and about 10% of clinical users will experience diarrhea. In order to study the mechanism of diarrhea, scientists used a new method of non-damage micro-testing technology combined with traditional methods to study the causes of diarrhea caused by entacapone.

In 2011, the Zhu Jinxia laboratory of the Capital Medical University used non-invasive micro-measurement technology to measure the flow rate of Cl-, short-circuit current (ISC) to measure the charged ion transport, and radioimmunoassay (RIA) to measure the intracellular cAMP content. It was found that entacapone increased ISC and Cl-secretion in the rat peripheral colonic mucosa, and the application of diphenylamine 2,2'-dicarboxylic acid (DPC) (a Cl-channel inhibitor) on the top significantly inhibited ISC, basal lateral The administration of bumetanide (Na + -K + -2Cl- (NLCC) co-transport inhibitor) significantly inhibited Cl-outflow. Indomethacin inhibits the synthesis of endogenous prostaglandins (PG), and reduces the activity of submucosal enteric nerves and tetrodotoxin (TTX) inhibited entacapone-induced increase of ISC and Cl- secretion.

Entacapone stimulates cAMP-dependent Cl-secretion in the rat colon, a process regulated by endogenous PG and the submucosal enteric nervous system. This study explains the reason why Ntacapone produces gastrointestinal incompatibility, that is, a large amount of Cl- secretion.

Keywords: Entacapone (Entacapone), ion secretion, non-damage micro-testing technology, short circuit current

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

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