1. Cholinesterases and the resistance of the mouse diaphragm to the effect of tubocurarine
- Author
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Tu Nguyen-Huu, Julien Barbier, Jordi Molgó, Alexandre Dobbertin, Philippe Duvaldestin, Eric Krejci, Jasmina Minic, Outters-Lafaye, Michèle, Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Biologie des Jonctions Neuromusculaires Normales et Pathologiques (U686), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Henri Mondor - Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
- Subjects
MESH : Neuromuscular Nondepolarizing Agents ,Drug Resistance ,Muscle Proteins ,Tubocurarine ,MESH : Dose-Response Relationship, Drug ,Receptors, Nicotinic ,MESH: Dose-Response Relationship, Drug ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,030202 anesthesiology ,MESH: Collagen ,COLQ ,Medicine ,MESH: Animals ,MESH : Tubocurarine ,MESH : Muscle Proteins ,biology ,musculoskeletal, neural, and ocular physiology ,Neuromuscular Blocking Agents ,musculoskeletal system ,Acetylcholinesterase ,Diaphragm (structural system) ,medicine.anatomical_structure ,Biochemistry ,MESH: Receptors, Nicotinic ,MESH: Drug Resistance ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Collagen ,tissues ,Acetylcholine ,medicine.drug ,medicine.medical_specialty ,Synaptic cleft ,Diaphragm ,Neuromuscular Junction ,In Vitro Techniques ,Neuromuscular junction ,MESH : Acetylcholinesterase ,03 medical and health sciences ,MESH: Muscle Proteins ,Internal medicine ,MESH : Mice ,Animals ,MESH: Tubocurarine ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Mice ,Cholinesterase ,MESH : Drug Resistance ,MESH : Receptors, Nicotinic ,Dose-Response Relationship, Drug ,business.industry ,MESH: Acetylcholinesterase ,Anesthesiology and Pain Medicine ,Endocrinology ,chemistry ,MESH: Diaphragm ,MESH : Collagen ,biology.protein ,MESH : Neuromuscular Junction ,MESH : Animals ,MESH: Neuromuscular Junction ,MESH : Diaphragm ,business ,MESH: Neuromuscular Nondepolarizing Agents ,030217 neurology & neurosurgery ,Neuromuscular Nondepolarizing Agents - Abstract
Background The diaphragm is resistant to competitive neuromuscular blocking agents. Because of the competitive mechanism of action of tubocurarine, the rate of hydrolysis of acetylcholine at the neuromuscular junction may modulate its neuromuscular blocking effect. The authors compared the neuromuscular blocking effect of tubocurarine on isolated diaphragm and extensor digitorum longus (EDL) muscles and quantified the acetylcholinesterase activity in hetero-oligomers. Methods Adult Swiss-Webster and collagen Q-deficient (ColQ) mice were used. The blocking effect of tubocurarine on nerve-evoked muscle twitches was determined in isolated diaphragm and EDL muscles, after inhibition of acetylcholinesterase by fasciculin-1, butyrylcholinesterase by tetraisopropylpyro-phosphoramide, or both acetylcholinesterase and butyrylcholinesterase by neostigmine, and in acetylcholinesterase-deficient ColQ muscles. The different acetylcholinesterase oligomers extracted from diaphragm and EDL muscles were quantified in sucrose gradient. Results The EC50 for tubocurarine to decrease the nerve-evoked twitch response was four times higher in the diaphragm than in the EDL. The activity of the different acetylcholinesterase oligomers was lower in the diaphragm as compared with the EDL. Inhibition of acetylcholinesterase by antagonists resulted in an increased dose of tubocurarine but an unchanged resistance ratio between the diaphragm and the EDL. A similar diaphragmatic resistance was found in ColQ muscles. Conclusion The current study indicates that, despite differences in acetylcholinesterase activity between the diaphragm and EDL, the diaphragmatic resistance to tubocurarine cannot be explained by the different rate of acetylcholine hydrolysis in the synaptic cleft.
- Published
- 2005