Darifenacin reveals a functional role for M4 muscarinic acetylcholine receptors in guinea pig gallbladder

Ahmet Akici, Muradiye Nacak, Arthur Christopoulos, Şule Oktay

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: Previous studies have revealed the presence of M1 to M4 muscarinic receptors in guinea pig gallbladder, with M 3 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 μM, 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 current findings provide pharmacological evidence for a predominant role of M4 muscarinic receptors in guinea pig gallbladder contractions.

Original languageEnglish
Pages (from-to)248-252
Number of pages5
JournalMarmara Medical Journal
Volume15
Issue number4
Publication statusPublished - 1 Oct 2002
Externally publishedYes

Keywords

  • Contraction
  • Darifenacin
  • Gallbladder
  • Guinea-pig
  • Muscarinic receptor

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