D Alvarez-Berdugo1, F Espín1, C Arenas2, I López1, P Clavé1,2,3, D Gallego2. 1. Gastrointestinal Physiology Laboratory, Department of Surgery, Hospital de Mataró, Universitat Autònoma de Barcelona, Barcelona, Spain. 2. Centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas CIBERehd, Instituto de Salud Carlos III, Barcelona, Spain. 3. Health Sciences Research Institute of the Germans Trias i Pujol Foundation, Barcelona, Spain.
Abstract
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 NK2 antagonist GR94800) 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 M2 , M3 , NK2 receptors and L-type calcium channels. KEY RESULTS: Contractions to carbachol (Emax : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS; p < 0.0005) and NKA (Emax : 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 (pIC50 = 8.56 ± 0.15 control vs pIC50 = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR94800 (pIC50 = 7.21 ± 0.18 control vs pIC50 = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency (pIC50 ) 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 NK2 antagonists observed in DS might play a role in the spasticity found in diverticular disease.
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 NK2 antagonist GR94800) 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 M2 , M3 , NK2 receptors and L-type calcium channels. KEY RESULTS: Contractions to carbachol (Emax : 663.7 ± 305.6% control vs 2698.0 ± 439.5% DS; p < 0.0005) and NKA (Emax : 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 (pIC50 = 8.56 ± 0.15 control vs pIC50 = 9.95 ± 0.18 DS group; p < 0.005) and slightly higher for GR94800 (pIC50 = 7.21 ± 0.18 control vs pIC50 = 7.97 ± 0.32 group; p < 0.0001). Lower efficacy (Emax ) and potency (pIC50 ) 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 NK2 antagonists observed in DS might play a role in the spasticity found in diverticular disease.
Authors: Maria Raffaella Barbaro; Cesare Cremon; Daniele Fuschi; Giovanni Marasco; Marta Palombo; Vincenzo Stanghellini; Giovanni Barbara Journal: Int J Mol Sci Date: 2022-06-15 Impact factor: 6.208