Abstract |
Nicotinic receptor (nAChR) subtypes involved in pre- and postjunctional actions underlying tetanic fade were studied in rat phrenic-nerve hemidiaphragms. We investigated the ability of subtype-specific nAChR antagonists to depress nerve-evoked contractions and [(3)H]- acetylcholine ([(3)H]-ACh) release. Muscle tension was transiently increased during brief high frequency trains (50 Hz for 5 sec). The rank potency order of nAChR antagonists to reduce tetanic peak tension was alpha-bungarotoxin > d-tubocurarine >> mecamylamine > hexamethonium. Reduction of maximal tetanic tension produced by dihydro-beta-erythroidine (0.03-10 microM), methyllycaconitine (0.003-3 microM), and alpha-conotoxin MII (0.001-0.3 microM) did not exceed 30%. Besides reduction of peak tension d-tubocurarine (0.1-0.7 microM), mecamylamine (0.1-300 microM), and hexamethonium (30-3,000 microM) also caused tetanic fading. With alpha-conotoxin MII (0.001-0.3 microM) and dihydro-beta-erythroidine (0.03-10 microM), tetanic fade was evident only after decreasing the safety factor of neuromuscular transmission (with high magnesium ions, 6-7 mM). The antagonist rank potency order to reduce evoked (50 Hz for 5 sec) [(3)H]-ACh release from motor nerve terminals was alpha-conotoxin MII (0.1 microM) > dihydro-beta-erythroidine (1 microM) approximately d-tubocurarine (1 microM) > mecamylamine (100 microM) > hexamethonium (1,000 microM). When applied in a concentration (0.3 microM) above that producing tetanic paralysis, alpha-bungarotoxin failed to affect [(3)H]-ACh release. Data obtained suggest that postjunctional neuromuscular relaxants interact with alpha-bungarotoxin-sensitive nicotinic receptors containing alpha1-subunits, whereas blockade of neuronal alpha3beta2-containing receptors produce tetanic fade by breaking nicotinic autofacilitation of acetylcholine release.
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Authors | Miguel Faria, Laura Oliveira, M Alexandrina Timóteo, M Graça Lobo, Paulo Correia-De-Sá |
Journal | Synapse (New York, N.Y.)
(Synapse)
Vol. 49
Issue 2
Pg. 77-88
(Aug 2003)
ISSN: 0887-4476 [Print] United States |
PMID | 12740863
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2003 Wiley-Liss, Inc. |
Chemical References |
- Nicotinic Antagonists
- Receptors, Nicotinic
- nicotinic receptor alpha3beta2
- Acetylcholine
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Topics |
- Acetylcholine
(metabolism)
- Animals
- Diaphragm
(drug effects, metabolism, physiology)
- Dose-Response Relationship, Drug
- Female
- Male
- Muscle Contraction
(drug effects, physiology)
- Neurons
(drug effects, physiology)
- Nicotinic Antagonists
(pharmacology)
- Rats
- Rats, Wistar
- Receptors, Nicotinic
(physiology)
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