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Changes in the response to excitatory antagonists, agonists, and spasmolytic agents in circular colonic smooth muscle strips from patients with diverticulosis
Author(s) -
AlvarezBerdugo D.,
Espín F.,
Arenas C.,
López I.,
Clavé P.,
Gallego D.
Publication year - 2015
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12659
Subject(s) - medicine , excitatory postsynaptic potential , endocrinology , carbachol , atropine , stimulation , antagonist , chemistry , receptor
Background 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 . Methods Circular muscle strips from sigmoid colon of DS patients ( n = 30; 69.5 ± 14.8 years) and controls ( n = 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 2 antagonist GR 94800) and spasmolytic drugs (otilonium bromide [ OB ] and N ‐butyl‐hyoscine) on the contractions induced by EFS ‐stimulation of excitatory motorneurons. qRT ‐ PCR was also performed to compare mRNA expression of M 2 , M 3 , NK 2 receptors and L‐type calcium channels. Key Results Contractions to carbachol (E max : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS ; p < 0.0005) and NKA (E max : 387.8 ± 35.6% vs 1102.0 ± 190.1%; p < 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 50 = 8.56 ± 0.15 control vs pIC 50 = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR 94800 ( pIC 50 = 7.21 ± 0.18 control vs pIC 50 = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (E max ) and potency ( pIC 50 ) was observed for spasmolytic drugs in DS , whereas no differences were found regarding the relative expression of the receptors evaluated between groups. Conclusions & Inferences The greater response to cholinergic and tachykinergic agonists and greater potency for muscarinic and NK 2 antagonists observed in DS might play a role in the spasticity found in diverticular disease.