Cargando…
Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission
ATP, being a well-known universal high-energy compound, plays an important role as a signaling molecule and together with its metabolite adenosine they both attenuate the release of acetylcholine in the neuro-muscular synapse acting through membrane P2 and P1 receptors, respectively. In this work, u...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605505/ https://www.ncbi.nlm.nih.gov/pubmed/37886978 http://dx.doi.org/10.3390/cimb45100535 |
_version_ | 1785127090524258304 |
---|---|
author | Khairullin, Adel E. Grishin, Sergey N. Ziganshin, Ayrat U. |
author_facet | Khairullin, Adel E. Grishin, Sergey N. Ziganshin, Ayrat U. |
author_sort | Khairullin, Adel E. |
collection | PubMed |
description | ATP, being a well-known universal high-energy compound, plays an important role as a signaling molecule and together with its metabolite adenosine they both attenuate the release of acetylcholine in the neuro-muscular synapse acting through membrane P2 and P1 receptors, respectively. In this work, using a mechanomyographic method, we analyzed the presynaptic mechanisms by which ATP and adenosine can modulate the transduction in the rat m. soleus and m. extensor digitorum longus. N-ethylmaleimide, a G-protein antagonist, prevents the modulating effects of both ATP and adenosine. The action of ATP is abolished by chelerythrin, a specific phospholipase C inhibitor, while the inhibitory effect of adenosine is slightly increased by Rp-cAMPS, an inhibitor of protein kinase A, and by nitrendipine, a blocker of L-type Ca(2+) channels. The addition of DPCPX, an A(1) receptor antagonist, fully prevents the inhibitory action of adenosine in both muscles. Our data indicate that the inhibitory action of ATP involves metabotropic P2Y receptors and is mediated by phospholipase C dependent processes in rat motor neuron terminals. We suggest that the presynaptic effect of adenosine consists of negative and positive actions. The negative action occurs by stimulation of adenosine A(1) receptors while the positive action is associated with the stimulation of adenosine A(2A) receptors, activation of protein kinase A and opening of L-type calcium channels. The combined mechanism of the modulating action of ATP and adenosine provides fine tuning of the synapse to fast changing conditions in the skeletal muscles. |
format | Online Article Text |
id | pubmed-10605505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106055052023-10-28 Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission Khairullin, Adel E. Grishin, Sergey N. Ziganshin, Ayrat U. Curr Issues Mol Biol Article ATP, being a well-known universal high-energy compound, plays an important role as a signaling molecule and together with its metabolite adenosine they both attenuate the release of acetylcholine in the neuro-muscular synapse acting through membrane P2 and P1 receptors, respectively. In this work, using a mechanomyographic method, we analyzed the presynaptic mechanisms by which ATP and adenosine can modulate the transduction in the rat m. soleus and m. extensor digitorum longus. N-ethylmaleimide, a G-protein antagonist, prevents the modulating effects of both ATP and adenosine. The action of ATP is abolished by chelerythrin, a specific phospholipase C inhibitor, while the inhibitory effect of adenosine is slightly increased by Rp-cAMPS, an inhibitor of protein kinase A, and by nitrendipine, a blocker of L-type Ca(2+) channels. The addition of DPCPX, an A(1) receptor antagonist, fully prevents the inhibitory action of adenosine in both muscles. Our data indicate that the inhibitory action of ATP involves metabotropic P2Y receptors and is mediated by phospholipase C dependent processes in rat motor neuron terminals. We suggest that the presynaptic effect of adenosine consists of negative and positive actions. The negative action occurs by stimulation of adenosine A(1) receptors while the positive action is associated with the stimulation of adenosine A(2A) receptors, activation of protein kinase A and opening of L-type calcium channels. The combined mechanism of the modulating action of ATP and adenosine provides fine tuning of the synapse to fast changing conditions in the skeletal muscles. MDPI 2023-10-19 /pmc/articles/PMC10605505/ /pubmed/37886978 http://dx.doi.org/10.3390/cimb45100535 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khairullin, Adel E. Grishin, Sergey N. Ziganshin, Ayrat U. Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title | Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title_full | Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title_fullStr | Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title_full_unstemmed | Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title_short | Presynaptic Purinergic Modulation of the Rat Neuro-Muscular Transmission |
title_sort | presynaptic purinergic modulation of the rat neuro-muscular transmission |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605505/ https://www.ncbi.nlm.nih.gov/pubmed/37886978 http://dx.doi.org/10.3390/cimb45100535 |
work_keys_str_mv | AT khairullinadele presynapticpurinergicmodulationoftheratneuromusculartransmission AT grishinsergeyn presynapticpurinergicmodulationoftheratneuromusculartransmission AT ziganshinayratu presynapticpurinergicmodulationoftheratneuromusculartransmission |