ВЛИЯНИЕ АЛЛОСТЕРИЧЕСКОГО МОДУЛЯТОРА М5 ХОЛИНОРЕЦЕПТОРОВ VU 0238429 НА НЕРВНО-МЫШЕЧНУЮ ПЕРЕДАЧУ В ДИАФРАГМАЛЬНОЙ МЫШЦЕ МЫШИ
PDF

Ключевые слова

нервно-мышечный контакт
М5 холинорецептор
ацетилхолин
потенциал концевой пластинки
модуляция синаптической передачи
мышечное сокращение

Как цитировать

Ковязина, И. В., Хамидуллина , А. А., Федоров, Н. С., & Маломуж, А. И. (2021). ВЛИЯНИЕ АЛЛОСТЕРИЧЕСКОГО МОДУЛЯТОРА М5 ХОЛИНОРЕЦЕПТОРОВ VU 0238429 НА НЕРВНО-МЫШЕЧНУЮ ПЕРЕДАЧУ В ДИАФРАГМАЛЬНОЙ МЫШЦЕ МЫШИ. Российский физиологический журнал им. И. М. Сеченова, 108(1), 98–108. https://doi.org/10.31857/S0869813922010083

Аннотация

Исследовали влияние соединения VU 0238429, аллостерического модулятора мускариновых холинорецепторов М5 подтипа, на амплитудно-временные параметры спонтанных и вызванных потенциалов концевой пластинки, а также на силу мышечных сокращений при низко- и высокочастотном раздражении двигательного нерва. Показано, что холинорецепторы М5 подтипа могут регулировать квантовый выброс ацетилхолина из двигательных нервных окончаний в диафрагме мыши: увеличивать уровень секреции медиатора при низкочастотной стимуляции нерва и снижать его при стимуляции с частотой 70 Гц. Фармакологическая потенциация М5 холинорецепторов оказывает угнетающее действие на силу мышечных сокращений, вызванных как прямой, так и непрямой стимуляцией, что необходимо учитывать при разработке лекарственных препаратов на основе модуляторов этих рецепторов.

https://doi.org/10.31857/S0869813922010083
PDF

Литература

Wess J, Eglen RM, Gautam D (2007) Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov 6:721–733. https://doi.org/10.1038/nrd2379

Yamada M, Basile AS, Fedorova I, Zhang W, Duttaroy A, Cui Y, Lamping KG, Faraci FM, Deng CX, Wess J (2003) Novel insights into M5 muscarinic acetylcholine receptor function by the use of gene targeting technology. Life Sci 74:345–353. https://doi.org/10.1016/j.lfs.2003.09.022

Langmead CJ, Watson J, Reavill C (2008) Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol Ther 117:232–243. s://doi.org/10.1016/j.pharmthera.2007.09.009

Araya R, Noguchi T, Yuhki M, Kitamura N, Higuchi M, Saido TC, Seki K, Itohara S, Kawano M, Tanemura K, Takashima A, Yamada K, Kondoh Y, Kanno I, Wess J, Yamada M (2006) Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice. Neurobiol Dis 24:334–344. https://doi.org/10.1016/j.nbd.2006.07.010

Wright MC, Potluri S, Wang X, Dentcheva E, Gautam D, Tessler A, Wess J, Rich MM, Son YJ (2009) Distinct muscarinic acetylcholine receptor subtypes contribute to stability and growth, but not compensatory plasticity, of neuromuscular synapses. J Neurosci 29:14942–14955. s://doi.org/10.1523/jneurosci.2276-09.2009

Tsentsevitsky AN, Kovyazina IV, Nurullin LF, Nikolsky EE (2017) Muscarinic cholinoreceptors (M1-, M2-, M3- and M4-type) modulate the acetylcholine secretion in the frog neuromuscular junction. Neurosci Lett 649:62–69. https://doi.org/10.1016/j.neulet.2017.04.015

Bridges TM, Marlo JE, Niswender CM, Jones CK, Jadhav SB, Gentry PR, Plumley HC, Weaver CD, Conn PJ, Lindsley CW (2009) Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins. J Med Chem 52:3445-3448. https://doi.org/10.1021/jm900286j

Ruiz R, Cano R, Casañas JJ, Gaffield MA, Betz WJ, Tabares L (2011) Active zones and the readily releasable pool of synaptic vesicles at the neuromuscular junction of the mouse. J Neurosci 31:2000-2008. s://doi.org/10.1523/JNEUROSCI.4663-10.2011

Nathanson NM (2008) Synthesis, trafficking, and localization of muscarinic acetylcholine receptors. Pharmacol Ther 119: 33–43. s://doi.org/10.1016/j.pharmthera.2008.04.006

Malomouzh AI, Mukhtarov MR, Nikolsky EE, Vyskočil F (2007) Muscarinic M1 acetylcholine receptors regulate the non-quantal release of acetylcholine in the rat neuromuscular junction via NO-dependent mechanism. J Neurochem 102:2110–2117. https://doi.org/10.1111/j.1471-4159.2007.04696.x

Tsentsevitsky AN, Zakyrjanova GF, Petrov AM, Kovyazina IV (2020) Breakdown of phospholipids and the elevated nitric oxide are involved in M3 muscarinic regulation of acetylcholine secretion in the frog motor synapse. Biochem Biophys Res Commun 524: 589–594. s://doi.org/10.1016/j.bbrc.2020.01.112

Garcia N, Santafé MM, Salon I, Lanuza MA, Tomàs J (2005) Expression of muscarinic acetylcholine receptors (M1-, M2-, M3- and M4-type) in the neuromuscular junction of the newborn and adult rat. Histol Histopathol 20:733–743. s://doi.org/10.14670/HH-20.733

Oliveira L, Timóteo MA, Correia-de-Sá P (2009) Negative crosstalk between M1 and M2 muscarinic autoreceptors involves endogenous adenosine activating A1 receptors at the rat motor endplate. Neurosci Lett 459:127–131. https://doi.org/10.1016/j.neulet.2009.05.001

Levey AI (1993) Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. Life Sci 52:441–448. s://doi.org/10.1016/0024-3205(93)90300-r

Bukharaeva EA, Kim KK, Nikol'skii EE, Vyskochil F (2000) Synchronization of evoked secretion of quanta of mediator as a mechanism facilitating the action of sympathomimetics. Neurosci Behav Physiol 30:139–146. https://doi.org/10.1007/BF02463151

Malomouzh AI, Arkhipova SS, Nikolsky EE, Vyskočil F (2011) Immunocytochemical demonstration of M(1) muscarinic acetylcholine receptors at the presynaptic and postsynaptic membranes of rat diaphragm endplates. Physiol Res 60:185–188. https://doi.org/10.33549/physiolres.932131

Newman Z, Malik P, Wu TY, Ochoa C, Watsa N, Lindgren C (2007) Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction. Eur J Neurosci 25:1619–1630. s://doi.org/10.1111/j.1460-9568.2007.05422.x

Felder CC, Ma AL, Briley EM, Axelrod J (1993) Muscarinic acetylcholine receptor subtypes associated with release of Alzheimer amyloid precursor derivatives activate multiple signal transduction pathways. Ann NY Acad Sci 695:15–18. https://doi.org/10.1111/j.1749-6632.1993.tb23020.x

Guo J, Schofield GG (2003) Activation of muscarinic m5 receptors inhibits recombinant KCNQ2/KCNQ3 K+ channels expressed in HEK293T cells. Eur J Pharmacol 462:25–32. s://doi.org/10.1016/s0014-2999(03)01323-2

Cumbay MG, Watts VJ (2005) Galphaq potentiation of adenylate cyclase type 9 activity through a Ca2+/calmodulin-dependent pathway. Biochem Pharmacol 69:1247–1256. https://doi.org/10.1016/j.bcp.2005.02.001

Cantrell AR, Ma JY, Scheuer T, Catterall WA (1996) Muscarinic modulation of sodium current by activation of protein kinase C in rat hippocampal neurons. Neuron 16:1019–1026. s://doi.org/10.1016/s0896-6273(00)80125-7

Pemberton KE, Jones SV (1997) Inhibition of the L-type calcium channel by the five muscarinic receptors (m1-m5) expressed in NIH 3T3 cells. Pflugers Arch 433:505-514. https://doi.org/10.1007/s004240050306

Mitchell JF, Silver A (1963) The spontaneous release of acetylcholine from the denervated hemidiaphragm of the rat. J Physiol 165:117–129. https://doi.org/10.1113/jphysiol.1963.sp007046

Krnjevic K, Straughan DW (1964) The release of acetylcholine from the denervated rat diaphragm. J Physiol 170:371–378. s://doi.org/10.1113/jphysiol.1964.sp007337

Molenaar PC, Polak RL (1980) Acetylcholine synthesizing enzymes in frog skeletal muscle. J Neurochem 35:1021–1025. s://doi.org/10.1111/j.1471-4159.1980.tb07855.x

Tucek S (1982) The synthesis of acetylcholine in skeletal muscles of the rat. J Physiol 322:53–69. s://doi.org/10.1113/jphysiol.1982.sp014022

Krivoi II (2002) Mechanisms of the non-neurotransmitter actions of acetylcholine in the neuromuscular apparatus. Neurosci Behav Physiol 32:149–156. https://doi.org/10.1023/a:1013975324963

Vyskocil F, Malomouzh AI, Nikolsky EE (2009) Non-quantal acetylcholine release at the neuromuscular junction. Physiol Res 58:763–784. https://doi.org/10.33549/physiolres.931865