Effects of VU 0238429, an Allosteric Modulator of M5 Cholinoreceptors, on Neuromuscular Transmission in the Mouse Diaphragm
The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M 5 receptor, on the amplitude and temporal parameters of spontaneous and evoked endplate potentials, as well as on the force of muscle contractions in different modes of motor nerve stimulation, were studied. It wa...
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| Published in | Journal of evolutionary biochemistry and physiology Vol. 58; no. 1; pp. 149 - 157 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
Moscow
Pleiades Publishing
2022
Springer Nature B.V |
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| Abstract | The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M
5
receptor, on the amplitude and temporal parameters of spontaneous and evoked endplate potentials, as well as on the force of muscle contractions in different modes of motor nerve stimulation, were studied. It was shown that M
5
cholinoreceptors regulate the quantal release of acetylcholine from motor nerve endings in the mouse diaphragm. Specifically, M
5
activation increases the level of ACh release during low-frequency nerve stimulation (0.5 Hz) and enhances synaptic depression at 70 Hz. Pharmacological potentiation of M
5
cholinoreceptors exerts a depressing effect on the force of skeletal muscle contractions at stimulation frequencies in the range from 0.5 to 70 Hz, which must be considered when developing new drugs aimed at affecting M
5
cholinoreceptors. |
|---|---|
| AbstractList | The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M5 receptor, on the amplitude and temporal parameters of spontaneous and evoked endplate potentials, as well as on the force of muscle contractions in different modes of motor nerve stimulation, were studied. It was shown that M5 cholinoreceptors regulate the quantal release of acetylcholine from motor nerve endings in the mouse diaphragm. Specifically, M5 activation increases the level of ACh release during low-frequency nerve stimulation (0.5 Hz) and enhances synaptic depression at 70 Hz. Pharmacological potentiation of M5 cholinoreceptors exerts a depressing effect on the force of skeletal muscle contractions at stimulation frequencies in the range from 0.5 to 70 Hz, which must be considered when developing new drugs aimed at affecting M5 cholinoreceptors. The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M 5 receptor, on the amplitude and temporal parameters of spontaneous and evoked endplate potentials, as well as on the force of muscle contractions in different modes of motor nerve stimulation, were studied. It was shown that M 5 cholinoreceptors regulate the quantal release of acetylcholine from motor nerve endings in the mouse diaphragm. Specifically, M 5 activation increases the level of ACh release during low-frequency nerve stimulation (0.5 Hz) and enhances synaptic depression at 70 Hz. Pharmacological potentiation of M 5 cholinoreceptors exerts a depressing effect on the force of skeletal muscle contractions at stimulation frequencies in the range from 0.5 to 70 Hz, which must be considered when developing new drugs aimed at affecting M 5 cholinoreceptors. |
| Author | Fedorov, N. S. Malomouzh, A. I. Kovyazina, I. V. Khamidullina, A. A. |
| Author_xml | – sequence: 1 givenname: I. V. surname: Kovyazina fullname: Kovyazina, I. V. email: irina.kovyazina@list.ru organization: Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center, Russian Academy of Sciences, Department of Medical and Biological Physics, Kazan State Medical University – sequence: 2 givenname: A. A. surname: Khamidullina fullname: Khamidullina, A. A. organization: Department of Medical and Biological Physics, Kazan State Medical University – sequence: 3 givenname: N. S. surname: Fedorov fullname: Fedorov, N. S. organization: Kazan Federal University – sequence: 4 givenname: A. I. surname: Malomouzh fullname: Malomouzh, A. I. email: artur57@gmail.com organization: Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center, Russian Academy of Sciences |
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| Cites_doi | 10.1016/j.neulet.2017.04.015 10.33549/physiolres.931865 10.1111/j.1749-6632.1993.tb23020.x 10.1016/0024-3205(93)90300-r 10.1016/j.pharmthera.2007.09.009 10.1016/j.lfs.2003.09.022 10.1113/jphysiol.1963.sp007046 10.1038/nrd2379 10.1523/jneurosci.2276-09.2009 10.1113/jphysiol.1982.sp014022 10.1523/JNEUROSCI.4663-10.2011 10.1016/j.bbrc.2020.01.112 10.1007/BF02463151 10.1016/j.pharmthera.2008.04.006 10.1007/s004240050306 10.1016/j.bcp.2005.02.001 10.1111/j.1471-4159.2007.04696.x 10.1016/s0896-6273(00)80125-7 10.1111/j.1460-9568.2007.05422.x 10.1016/s0014-2999(03)01323-2 10.1021/jm900286j 10.33549/physiolres.932131 10.1016/j.nbd.2006.07.010 10.1023/a:1013975324963 10.1016/j.neulet.2009.05.001 10.1111/j.1471-4159.1980.tb07855.x 10.14670/HH-20.733 10.1113/jphysiol.1964.sp007337 |
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| Keywords | muscle contraction neuromuscular junction muscarinic M cholinoreceptor acetylcholine modulation of synaptic transmission endplate potential |
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| Snippet | The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M
5
receptor, on the amplitude and temporal parameters of spontaneous and... The effects of VU 0238429, an allosteric modulator of muscarinic acetylcholine (ACh) M5 receptor, on the amplitude and temporal parameters of spontaneous and... |
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| SubjectTerms | Acetylcholine Acetylcholine receptors (muscarinic) Allosteric properties Animal Physiology Biochemistry Biomedical and Life Sciences Diaphragm Evolutionary Biology Experimental Papers Life Sciences Muscle contraction Nerve endings Neuromuscular junctions Potentiation Quantal release Skeletal muscle Synaptic depression |
| Title | Effects of VU 0238429, an Allosteric Modulator of M5 Cholinoreceptors, on Neuromuscular Transmission in the Mouse Diaphragm |
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