Effects of VU 0238429, an Allosteric Modulator of M5 Cholinoreceptors, on Neuromuscular Transmission in the Mouse Diaphragm

• Published in: Journal of evolutionary biochemistry and physiology Vol. 58; no. 1; pp. 149 - 157
• Main Authors: Kovyazina, I. V., Khamidullina, A. A., Fedorov, N. S., Malomouzh, A. I.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 2022; Springer Nature B.V
• Subjects: 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; muscle contraction; neuromuscular junction; muscarinic M; cholinoreceptor; acetylcholine; modulation of synaptic transmission; endplate potential
• ISSN: 0022-0930; 1608-3202
• DOI: 10.1134/S0022093022010136

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.