Neuromuscular facilitation induced by muscarinic antagonists in the rat isolated diaphragm.
1. Atropine (EC50 = 87 microM), pirenzepine (447 microM), and AF-DX 116 (95.5 microM), but not 4-DAMP (at concentrations of up to 110 microM), produced neuromuscular facilitation and antagonized the oxotremorine-induced neuromuscular blockade in the rat isolated diaphragm. 2. Atropine, pirenzepine, and AF-DX 116 did not change the responses of curarized diaphragms to direct stimulation, or the twitch tension produced by retrograde injection of acetylcholine. 3. These results indicate that neuromuscular facilitation induced by muscarinic antagonists may depend on drug interaction with the M2 subtype of muscarinic autoreceptors to increase acetylcholine output in the neuromuscular junction.
Alves-do-Prado
W
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Department of Pharmacology, University of Maringá, PR, Brazil.
Prado
W A
WA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists; D009469:Neuromuscular Junction / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology*; D010791:Phrenic Nerve / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D000109:Acetylcholine