Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice
Abstract
:1. Introduction
2. Adenylyl Cyclase Inhibition and Phosphoinositide Hydrolysis
3. Muscarinic Regulation of Ion Channel Activity
3.1. Activation of Non-Selective Cationic Channels
3.2. Regulation of K+ and Cl− Channels
3.3. Inhibition of Voltage-Dependent Ca2+ Channels
4. Depolarisation
5. Ca2+ Sensitisation of Contraction
6. Heterologous Desensitisation of Contraction
7. Smooth Muscle Contraction
7.1. Contraction Evoked by Applied Muscarinic Agonists
7.2. Cholinergic Nerve-Mediated Contraction
7.3. Indirect Contraction by Inhibiting Cyclic AMP-Dependent Relaxation
7.4. Muscarinic Contractile Mechanisms in Mouse Intestinal Smooth Muscle
8. In Vivo and In Vitro Gastrointestinal Motility
9. Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACh | acetylcholine |
BK channels | large conductance Ca2+-activated K+ channels |
[Ca2+]i | intracellular Ca2+ concentration |
cAMP | cyclic AMP |
DAG | diacylglycerol |
EC50 | 50% effective concentration |
EFS | electrical field stimulation |
EJP | excitatory junction potential |
Emax | maximum response |
G-proteins | GTP binding proteins |
Ica | Ca2+ current |
ICCs | interstitial cells of Cajal |
InsP3 | inositol 1,4,5-trisphosphate |
KATP channels | ATP-sensitive K+ channels |
KO | knockout |
mIcat | mAChR-mediated cationic current |
muscarinic acetylcholine receptors | mAChRs |
NO | nitric oxide |
NPY | neuropeptide Y |
pEC50 | negative logarithm of EC50 |
PGF2α | prostaglandin F2α |
PIP2 | phosphatidylinositol 4,5-bisphosphate |
PKC | protein kinase C |
PLC | phospholipase C |
PTX | pertussis toxin |
RASSL | Receptor Solely by Synthetic Ligand |
STOCs | spontaneous transient outward currents |
TRPC channels | Transient receptor potential canonical channels |
VDCCs | voltage-dependent Ca2+ channels |
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Tissue | Protocol/Agonist b | Emax (% of Wild Type) a | References | |||
---|---|---|---|---|---|---|
M2-KO | M3-KO | M2/M3-KO | M4-KO | |||
Stomach fundus | Cumulative/CCh | 96 | 44 * | 95 | Stengel et al. (2000; 2002) [80,81] | |
Single dose/CCh | 102 | 66 * | 0 (relax.) | Kitazawa et al. (2007) [82] | ||
Cumulative/CCh | 114 | 49 * | 0 (relax.) | Kitazawa et al. (2007) [82] | ||
Stomach antrum | Single dose/CCh | 84 | 64 * | 0 (relax.) | Kitazawa et al. (2007) [82] | |
Cumulative/CCh | 86 | 57 * | 0 (relax.) | Kitazawa et al. (2007) [82] | ||
Stomach body | Cumulative/CCh | 95 | 42 * | Ruggieri and Braverman (2013) [83] | ||
Ileum | Cumulative/CCh | 75 | 25 | 0 | Matsui et al. (2000; 2002) [84,85] | |
Cumulative/Oxo.M | 98 | Matsui et al. (2003) [86] | ||||
Single dose/CCh | 103 | 62 * | 0 (relax.) | Unno et al. (2005) [87] | ||
Single dose/ACh | 102 | 43 | Takeuchi et al. (2007) [88] | |||
Cumulative/Oxo.M | 101 | 36 * | Griffin et al. (2009) [89] | |||
Colon proximal | Single dose/CCh | 66 * | 34 | 0 (relax.) | Kondo et al. (2011) [90] | |
Colon distal | Single dose/CCh | 65 * | 21 | 0 (relax.) | Kondo et al. (2011) [90] | |
Trachea | Cumulative/CCh | 86 * | 44 * | 82 | Stengel et al. (2000; 2002) [80,81] | |
Cumulative/Oxo.M | 88 | Matsui et al. (2003) [86] | ||||
Gallbladder | Cumulative/CCh | 79 | 21 | 100 | Stengel and Cohen (2002) [91] | |
Urinary bladder | Cumulative/CCh | 95 | 5 | 0 | Matsui et al. (2000; 2002) [84,85] | |
Cumulative/Oxo.M | 84 | Matsui et al. (2003) [86] | ||||
Cumulative/CCh | 82 | 6 * | 97 | Stengel et al. (2000; 2002) [80,81] | ||
Cumulative/Oxo.M | 89 | 15 * | 0 | Ehlert et al. (2005) [92] | ||
Single dose/CCh | 77 * | 7 * | 0 | # | ||
Uterus | Cumulative/CCh | 66 * | 0 | 0 | Kitazawa et al. (2008) [93] |
Tissue | Protocol/Agonist | pEC50 | References | ||
---|---|---|---|---|---|
Wild Type: M2-KO | Wild Type: M3-KO | Wild Type: M4-KO | |||
Stomach fundus | Cumulative/CCh | 6.68:6.39 * | 6.54:6.71 | 6.76:6.70 | Stengel et al. (2000; 2002) [80,81] |
Single dose/CCh | 6.93:6.51 * | 7.03:6.97 | Kitazawa et al. (2007) [82] | ||
Cumulative/CCh | 6.56:6.18 * | 6.67:6.73 | Kitazawa et al. (2007) [82] | ||
Stomach antrum | Single dose/CCh | 6.60:6.20 * | 6.50:6.90 | Kitazawa et al. (2007) [82] | |
Cumulative/CCh | 6.82:6.08 * | 6.92:7.10 | Kitazawa et al. (2007) [82] | ||
Stomach body | Cumulative/CCh | 6.1:5.7 * | 6.1:6.5 * | Ruggieri and Braverman (2013) [83] | |
Ileum | Single dose/CCh | 6.39:5.93 * | 6.14:6.18 | Unno et al. (2005) [87] | |
Cumulative/Oxo.M | 6.75:6.26 * | 6.75:6.99 * | Griffin et al., (2009) [89] | ||
Cumulative/Oxo.M | 6.70:6.38 * | Matsui et al. (2003) [86] | |||
Colon proximal | Single dose/CCh | 6.90:6.34 * | Kondo et al. (2011) [90] | ||
Colon distal | Single dose/CCh | 5.90:6.03 | Kondo et al. (2011) [90] | ||
Trachea | Cumulative/CCh | 6.56:6.27 * | 6.52:6.51 | 6.46:6.62 | Stengel et al. (2000; 2002) [80,81] |
Cumulative/Oxo.M | 6.94:6.86 | Matsui et al. (2003) [86] | |||
Urinary bladder | Cumulative/CCh | 6.27:6.07 * | 6.02:5.71 * | 6.30:6.20 | Stengel et al. (2000; 2002) [80,81] |
Cumulative/Oxo.M | 6.54:6.31 * | 6.54:6.60 | Ehlert et al. (2005) [92] | ||
Cumulative/Oxo.M | 6.58:6.41 | Matsui et al. (2003) [86] | |||
Single dose/CCh | 6.22:5.96 | 6.22:6.10 | # |
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Tanahashi, Y.; Komori, S.; Matsuyama, H.; Kitazawa, T.; Unno, T. Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice. Int. J. Mol. Sci. 2021, 22, 926. https://doi.org/10.3390/ijms22020926
Tanahashi Y, Komori S, Matsuyama H, Kitazawa T, Unno T. Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice. International Journal of Molecular Sciences. 2021; 22(2):926. https://doi.org/10.3390/ijms22020926
Chicago/Turabian StyleTanahashi, Yasuyuki, Seiichi Komori, Hayato Matsuyama, Takio Kitazawa, and Toshihiro Unno. 2021. "Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice" International Journal of Molecular Sciences 22, no. 2: 926. https://doi.org/10.3390/ijms22020926
APA StyleTanahashi, Y., Komori, S., Matsuyama, H., Kitazawa, T., & Unno, T. (2021). Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice. International Journal of Molecular Sciences, 22(2), 926. https://doi.org/10.3390/ijms22020926