The nature of the presynaptic effects of (+)-tubocurarine at the mouse neuromuscular junction. 1988

C B Ferry, and S S Kelly
Pharmacological Laboratories, Aston University, Birmingham.

1. The effects of (+)-tubocurarine (TC) on tetanic run-down and quantum content of end-plate potentials (EPPs) were investigated in cut-fibre preparations of mouse diaphragm. 2. (+)-Tubocurarine, 0.15 microM, halved the amplitude of spontaneous miniature EPPs (MEPPs) and steepened the tetanic run-down of EPPs evoked at 10 Hz by increasing the quantum content of the first EPP of the train while having no effect on quantum content of plateau EPPs. With stimulation at 1 Hz, there was little run-down and the quantum content of all EPPs was increased by TC. 3. The use of binomial statistics to analyse release indicated that after TC the increase in the quantum content of the first EPP in the train at 10 Hz was due to an increase in n and that during the run-down there was a decrease in p so that plateau EPP quantum content at 10 Hz was not different from control. 4. To elucidate a possible role of cholinoreceptors in the presynaptic effects of TC, studies were made on the effects of pancuronium or of alpha-bungarotoxin (BTX), with concentrations and exposure times where they had postsynaptic effects equal to 0.15 microM-TC. The run-down of EPPs was unaffected by BTX, while pancuronium steepened it to a lesser extent than TC. 5. The anticholinesterase, ecothiopate, decreased the quantum content of plateau EPPs only at high frequencies of stimulation (50 Hz) and did not affect the presynaptic effects of TC at 10 Hz. 6. At concentrations which reduced MEPP amplitude, atropine (10 microM) or hexamethonium (50 microM) had no effect on EPP run-down. 7. These results indicate that TC could have presynaptic effects via a presynaptic acetylcholine receptor, but that such a receptor may not have the same binding specificities as the postsynaptic receptor.

UI MeSH Term Description Entries
D008297 Male Males
D009045 Motor Endplate The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors. Motor End-Plate,End-Plate, Motor,End-Plates, Motor,Endplate, Motor,Endplates, Motor,Motor End Plate,Motor End-Plates,Motor Endplates
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D010197 Pancuronium A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release. Pancuronium Bromide,Pancuronium Curamed,Pancuronium Organon,Pavulon,Bromide, Pancuronium
D011950 Receptors, Cholinergic Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology. ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D002038 Bungarotoxins Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms. alpha-Bungarotoxin,beta-Bungarotoxin,kappa-Bungarotoxin,alpha Bungarotoxin,beta Bungarotoxin,kappa Bungarotoxin
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D004456 Echothiophate Iodide A potent, long-acting cholinesterase inhibitor used as a miotic in the treatment of glaucoma. Ecothiopate Iodide,2-((Diethoxyphosphinyl)thio)-N,N,N,-trimethylethanaminium iodide,Ecothiophate Iodide,Phospholine Iodide,Iodide, Echothiophate,Iodide, Ecothiopate,Iodide, Ecothiophate,Iodide, Phospholine
D000109 Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. 2-(Acetyloxy)-N,N,N-trimethylethanaminium,Acetilcolina Cusi,Acetylcholine Bromide,Acetylcholine Chloride,Acetylcholine Fluoride,Acetylcholine Hydroxide,Acetylcholine Iodide,Acetylcholine L-Tartrate,Acetylcholine Perchlorate,Acetylcholine Picrate,Acetylcholine Picrate (1:1),Acetylcholine Sulfate (1:1),Bromoacetylcholine,Chloroacetylcholine,Miochol,Acetylcholine L Tartrate,Bromide, Acetylcholine,Cusi, Acetilcolina,Fluoride, Acetylcholine,Hydroxide, Acetylcholine,Iodide, Acetylcholine,L-Tartrate, Acetylcholine,Perchlorate, Acetylcholine
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential

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