Using a novel analytical approach, we obtained a pKB estimate for darifenacin (7.51 ± 0.14) that is in excellent agreement with its affinity for M2/M4, but not M3 receptors.Conclusion: Given our previous demonstration that M2 receptors are unlikely to contribute to muscarinic contractions in this tissue, our currentfindings provide pharmacological evidence for a predominant role of M4 muscarinic receptors in guinea pig gallbladder contractions.Key Words: Muscarinic receptor, Guinea-pig, Gallbladder, Contraction, Darifenacin.
📌 3 Key Takeaways
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Objective & Hypothesis:Objective: Previous studies have revealed the presence of M1 to M4 muscarinic receptors in guinea pig gallbladder, with M3 and M4 receptors being claimed to mediate contractions.Methods: In the present study, cumulative concentration-response curves to carbachol were constructed in the absence and presence of darifenacin, which has greater selectivity for M3 over M4 receptors, in guinea-pig gallbladder.Results: Darifenacin caused concentration- dependent dextral shifts of the carbachol curve, however, at 1 pM, it also caused a degree of insurmountable antagonism.
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Key Findings & Data:Objective: Previous studies have revealed the presence of M1 to M4 muscarinic receptors in guinea pig gallbladder, with M3 and M4 receptors being claimed to mediate contractions.Methods: In the present study, cumulative concentration-response curves to carbachol were constructed in the absence and presence of darifenacin, which has greater selectivity for M3 over M4 receptors, in guinea-pig gallbladder.Results: Darifenacin caused concentration- dependent dextral shifts of the carbachol curve, however, at 1 pM, it also caused a degree of insurmountable antagonism.
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Conclusion & Impact:Using a novel analytical approach, we obtained a pKB estimate for darifenacin (7.51 ± 0.14) that is in excellent agreement with its affinity for M2/M4, but not M3 receptors.Conclusion: Given our previous demonstration that M2 receptors are unlikely to contribute to muscarinic contractions in this tissue, our currentfindings provide pharmacological evidence for a predominant role of M4 muscarinic receptors in guinea pig gallbladder contractions.Key Words: Muscarinic receptor, Guinea-pig, Gallbladder, Contraction, Darifenacin.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters
Abstract
Objective: Previous studies have revealed the presence of M1 to M4 muscarinic receptors in guinea pig gallbladder, with M3 and M4 receptors being claimed to mediate contractions.Methods: In the present study, cumulative concentration-response curves to carbachol were constructed in the absence and presence of darifenacin, which has greater selectivity for M3 over M4 receptors, in guinea-pig gallbladder.Results: Darifenacin caused concentration- dependent dextral shifts of the carbachol curve, however, at 1 pM, it also caused a degree of insurmountable antagonism. Using a novel analytical approach, we obtained a pKB estimate for darifenacin (7.51 ± 0.14) that is in excellent agreement with its affinity for M2/M4, but not M3 receptors.Conclusion: Given our previous demonstration that M2 receptors are unlikely to contribute to muscarinic contractions in this tissue, our currentfindings provide pharmacological evidence for a predominant role of M4 muscarinic receptors in guinea pig gallbladder contractions.Key Words: Muscarinic receptor, Guinea-pig, Gallbladder, Contraction, Darifenacin.
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Cite This Article
AKICI, A., NACAK, M., CHRİSTOPOULOS, A., OKTAY, Ş. (2002). DARIFENACIN REVEALS A FUNCTIONAL ROLE FOR M4 MUSCARINIC ACETYLCHOLINE RECEPTORS IN GUINEA PIG GALLBLADDER. Marmara Medical Journal, Cilt: 15 - Sayı: 4, 248–252. https://ajindex.com/articles/284402
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