Entacapone promotes cAMP-dependent Cl-secretion in rats causing gastrointestinal discomfort
Entacapone is a widely used drug for Parkinson's disease (PD) and is an inhibitor of catechol-O-methyltransferase (COMT). However, entacapone has gastrointestinal side effects, and about 10% of clinical users have diarrhea. In order to study the mechanism of produce diarrhea, scientists used a new method to study the reasons for non entacapone cause diarrhea NMT technology combined with traditional methods. 2011, Bak Capital Medical University laboratory using NMT Determination of of Cl - flow rate, the short circuit current (ISC) transport of charged ions measured, radioimmunoassay method (RIA) determination of the intracellular cAMP content. It was found that entacapone increased ISC and Cl - secretion in the distal colon mucosa of rats, and the application of diphenylamine 2,2'-dicarboxylic acid (DPC) (a Cl-channel inhibitor) on the top significantly inhibited ISC, basolateral administration bumetanide (Na + - K + -2Cl - (NLCC) cotransporter inhibitor) significantly inhibited the like Cl - outflows. Indomethacin inhibits the synthesis of endogenous prostaglandins (PG) and reduces the activity of submucosal enteric nerves and the increase in ISC and Cl- secretion by entacamine, which is inhibited by tetrodotoxin (TTX). Entacapone stimulates the secretion of cAMP-dependent Cl- in the colon of rats, a process regulated by endogenous PG and the submucosal enteric nervous system. This study explains the reason why entacapone produces gastrointestinal tract insufficiency, namely Cl - large secretion. Keywords: Entacapone, ion secretion, non-invasive micro-measurement, short-circuit current References: Li LS, et al . Neurogastroenterology and Motility, 2011, 23(7): 657-e277. Full text download Entacapone promotes cAMP-dependent colonic C l - Secretion in rat entacapone promotes cAMP- dependent Cl - secretion in rat colon Abstract Plastic Sponge Bowls,Disposable Guidewire Bowl,Medical Plastic Sponge Bowls,Disposable Plastic Sponge Bowls ShaoXing SurgeCare Medical Products Co., Ltd. , https://www.sxsurgecaremedical.com
Background Entacapone is a promising drug used widely for the treatment of Parkinson'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 (I SC ) 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 I SC in the rat distal colon. I SC was inhibited significantby 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 I SC 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.