Changes in the response to excitatory antagonists, agonists, and spasmolytic agents in circular colonic smooth muscle strips from patients with diverticulosis. Issue 11 (24th August 2015)

• Record Type: Journal Article
• Authors: Alvarez‐Berdugo, D.; Espín, F.; Arenas, C.; López, I.; Clavé, P.; Gallego, D.
• Is Part Of: Neurogastroenterology & motility. Volume 27:Issue 11(2015:Nov.)
• Page Start: 1600
• Page End: 1612
• Publication Date: 2015-08-24
• Subjects: Gastrointestinal system -- Motility -- Periodicals; Gastrointestinal system -- Innervation -- Periodicals; 616.33
• DOI: 10.1111/nmo.12659
• Languages: English
• ISSNs: 1350-1925

Abstract

<abstract abstract-type="main" id="nmo12659-abs-0001"> <title>Abstract</title> <sec id="nmo12659-sec-0001" sec-type="section"> <title>Background</title> <p>Colonic samples from asymptomatic diverticulosis (DS) patients presented enhanced electrical field stimulation (EFS)‐contractions, in an earlier study of ours, suggesting increased endogenous responses. The aim of this study was to explore changes in excitatory neuromuscular transmission and to assess the pharmacodynamics of spasmolytic agents in DS.</p> </sec> <sec id="nmo12659-sec-0002" sec-type="section"> <title>Methods</title> <p>Circular muscle strips from sigmoid colon of DS patients (<italic>n</italic> = 30; 69.5 ± 14.8 years) and controls (<italic>n</italic> = 32; 64.7 ± 16.2 years) were studied using organ baths to evaluate the direct effect of excitatory agonists (carbachol, neurokinin A [NKA] and substance P [SP]), and the effect of antagonists (atropine and NK<sub>2</sub> antagonist GR94800) and spasmolytic drugs (otilonium bromide [OB] and <italic>N</italic>‐butyl‐hyoscine) on the contractions induced by EFS‐stimulation of excitatory motorneurons. qRT‐PCR was also performed to compare mRNA expression of M<sub>2</sub>, M<sub>3</sub>, NK<sub>2</sub> receptors and L‐type calcium channels.</p> </sec> <sec id="nmo12659-sec-0003" sec-type="section"> <title>Key Results</title> <p>Contractions to carbachol (E<sub>max</sub>: 663.7 ± 305.6% control <italic>vs</italic> 2698.0 ± 439.5% DS;<italic> p</italic> < 0.0005) and NKA (E<sub>max</sub>: 387.8 ± 35.6% <italic>vs</italic> 1102.0 ± 190.1%; <italic>p</italic> < 0.0005) were higher in DS group, without differences for SP. Higher potency for DS patients was observed in the concentration‐response curves for atropine (pIC<sub>50</sub> = 8.56 ± 0.15 control <italic>vs </italic>pIC<sub>50</sub> = 9.95 ± 0.18 DS group; <italic>p</italic> < 0.005) and slightly higher for GR94800 (pIC<sub>50</sub> = 7.21 ± 0.18 control <italic>vs </italic>pIC<sub>50</sub> = 7.97 ± 0.32 group; <italic>p</italic> < 0.0001). Lower efficacy (E<sub>max</sub>) and potency (pIC<sub>50</sub>) was observed for spasmolytic drugs in DS, whereas no differences were found regarding the relative expression of the receptors evaluated between groups.</p> </sec> <sec id="nmo12659-sec-0004" sec-type="section"> <title>Conclusions & Inferences</title> <p>The greater response to cholinergic and tachykinergic agonists and greater potency for muscarinic and NK<sub>2</sub> antagonists observed in DS might play a role in the spasticity found in diverticular disease.</p> </sec> </abstract>