1. Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase
- Author
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Vassilia Theodorou, Lionel Bueno, Jean Fioramonti, Sylvie Bradesi, Afifa Ait-Belgnaoui, Neuro-Gastroentérologie et Nutrition (NGN), Ecole supérieure d'agriculture de Purpan (ESAP)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
- Subjects
Restraint, Physical ,medicine.medical_specialty ,Contraction (grammar) ,Myosin light-chain kinase ,Colon ,[SDV]Life Sciences [q-bio] ,Action Potentials ,Pyridinium Compounds ,Naphthalenes ,Distension ,Capillary Permeability ,03 medical and health sciences ,0302 clinical medicine ,Stress, Physiological ,Internal medicine ,Hypersensitivity ,medicine ,Animals ,Drug Interactions ,Rats, Wistar ,Myosin-Light-Chain Kinase ,Edetic Acid ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Analysis of Variance ,0303 health sciences ,Dose-Response Relationship, Drug ,Electromyography ,business.industry ,Visceral pain ,Azepines ,Epithelium ,Rats ,Dose–response relationship ,Anesthesiology and Pain Medicine ,Endocrinology ,medicine.anatomical_structure ,Neurology ,Paracellular transport ,Hyperalgesia ,Immunology ,Female ,030211 gastroenterology & hepatology ,Neurology (clinical) ,medicine.symptom ,business - Abstract
Hypersensitivity to rectal or colonic distension characterizes most patients with IBS and increased gut permeability has been described in post-dysenteric IBS patients. However, no link has been established between these two events. The aim of this study was to determine (i) whether chemical blockade of stress-induced increase of colonic paracellular permeability by 2,4,6 triaminopyrimidine (TAP) affects the concomitant hypersensitivity to colonic distension, (ii) the role of epithelial cell contraction in the stress-induced increased permeability and hyperalgesia, using a myosin light chain kinase inhibitor (ML-7). The effect of acute partial restraint stress (PRS) on visceral sensitivity to colorectal distension (RD) was assessed by abdominal muscle electromyography. Colonic paracellular permeability was determined by measuring percentage of urinary 51Cr-EDTA recovery after intracolonic infusion. The effect of stress on both parameters was evaluated after TAP, ML-7 or vehicle pretreated animals. PRS significantly increased colonic paracellular permeability and the number of spike bursts for all volumes of RD applied compared to sham. TAP suppressed the stress-induced increase of colonic paracellular permeability and sensitivity to colonic distension. Similarly, ML-7 blocked the stress-induced increase of colonic paracellular permeability and sensitivity. Neither ML-7 nor TAP had any effect on both permeability and sensitivity in absence of stress. The increase of colonic permeability induced by PRS results from epithelial cell cytoskeleton contraction through myosin light chain kinase activation and this increase is responsible for stress-induced rectal hypersensitivity.
- Published
- 2005