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 language | English |
|---|---|
| Pages (from-to) | 248-252 |
| Number of pages | 5 |
| Journal | Marmara Medical Journal |
| Volume | 15 |
| Issue number | 4 |
| Publication status | Published - 1 Oct 2002 |
| Externally published | Yes |
Keywords
- Contraction
- Darifenacin
- Gallbladder
- Guinea-pig
- Muscarinic receptor
Cite this
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Darifenacin reveals a functional role for M4 muscarinic acetylcholine receptors in guinea pig gallbladder. / Akici, Ahmet; Nacak, Muradiye; Christopoulos, Arthur; Oktay, Şule.
In: Marmara Medical Journal, Vol. 15, No. 4, 01.10.2002, p. 248-252.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Darifenacin reveals a functional role for M4 muscarinic acetylcholine receptors in guinea pig gallbladder
AU - Akici, Ahmet
AU - Nacak, Muradiye
AU - Christopoulos, Arthur
AU - Oktay, Şule
PY - 2002/10/1
Y1 - 2002/10/1
N2 - 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.
AB - 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.
KW - Contraction
KW - Darifenacin
KW - Gallbladder
KW - Guinea-pig
KW - Muscarinic receptor
UR - http://www.scopus.com/inward/record.url?scp=0141684539&partnerID=8YFLogxK
M3 - Article
VL - 15
SP - 248
EP - 252
JO - Marmara Medical Journal
JF - Marmara Medical Journal
SN - 1019-1941
IS - 4
ER -