Fig. 1. Representative force recordings of guinea pig tracheal ring preparations suspended in organ baths illustrating allosteric effects of rapacuronium (Rap). In  A , rings were first precontracted twice with an increasing concentrations of acetylcholine, washed three times, and then exposed to 1–100 μm rapacuronium, resulting in an increase in force; after thorough washing (nine times), a repeat addition of 1–100 μm rapacuronium was without effect. (  B ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), an acetylcholine precontraction, and three washes, rapacuronium now increased force. (  C ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), a single 0.1-μm acetylcholine dose was added, and rapacuronium then resulted in increased force. These results illustrate that rapacuronium only increased baseline force in the presence of subthreshold concentrations of acetylcholine, consistent with a positive allosteric cooperativity with acetylcholine at the M3 muscarinic receptor. Illustrations are typical of at least five independent experiments for each condition. 

Fig. 1. Representative force recordings of guinea pig tracheal ring preparations suspended in organ baths illustrating allosteric effects of rapacuronium (Rap). In  A , rings were first precontracted twice with an increasing concentrations of acetylcholine, washed three times, and then exposed to 1–100 μm rapacuronium, resulting in an increase in force; after thorough washing (nine times), a repeat addition of 1–100 μm rapacuronium was without effect. (  B ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), an acetylcholine precontraction, and three washes, rapacuronium now increased force. (  C ) In the absence of acetylcholine precontraction, 1–100 μm rapacuronium was without effect; after thorough washing (nine times), a single 0.1-μm acetylcholine dose was added, and rapacuronium then resulted in increased force. These results illustrate that rapacuronium only increased baseline force in the presence of subthreshold concentrations of acetylcholine, consistent with a positive allosteric cooperativity with acetylcholine at the M3 muscarinic receptor. Illustrations are typical of at least five independent experiments for each condition. 

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