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      Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats

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          Abstract

          Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10–100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (K ATP channels), glibenclamide (200 μM), inhibited the ATP-induced relaxation and application of an opener of K ATP channels, nicorandil (50 μM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of K ATP channels.

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          Physiological roles and properties of potassium channels in arterial smooth muscle.

          This review examines the properties and roles of the four types of K+ channels that have been identified in the cell membrane of arterial smooth muscle cells. 1) Voltage-dependent K+ (KV) channels increase their activity with membrane depolarization and are important regulators of smooth muscle membrane potential in response to depolarizing stimuli. 2) Ca(2+)-activated K+ (KCa) channels respond to changes in intracellular Ca2+ to regulate membrane potential and play an important role in the control of myogenic tone in small arteries. 3) Inward rectifier K+ (KIR) channels regulate membrane potential in smooth muscle cells from several types of resistance arteries and may be responsible for external K(+)-induced dilations. 4) ATP-sensitive K+ (KATP) channels respond to changes in cellular metabolism and are targets of a variety of vasodilating stimuli. The main conclusions of this review are: 1) regulation of arterial smooth muscle membrane potential through activation or inhibition of K+ channel activity provides an important mechanism to dilate or constrict arteries; 2) KV, KCa, KIR, and KATP channels serve unique functions in the regulation of arterial smooth muscle membrane potential; and 3) K+ channels integrate a variety of vasoactive signals to dilate or constrict arteries through regulation of the membrane potential in arterial smooth muscle.
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            Inwardly rectifying potassium channels: their structure, function, and physiological roles.

            Inwardly rectifying K(+) (Kir) channels allow K(+) to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are seven Kir channel subfamilies that can be classified into four functional groups: classical Kir channels (Kir2.x) are constitutively active, G protein-gated Kir channels (Kir3.x) are regulated by G protein-coupled receptors, ATP-sensitive K(+) channels (Kir6.x) are tightly linked to cellular metabolism, and K(+) transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x). Inward rectification results from pore block by intracellular substances such as Mg(2+) and polyamines. Kir channel activity can be modulated by ions, phospholipids, and binding proteins. The basic building block of a Kir channel is made up of two transmembrane helices with cytoplasmic NH(2) and COOH termini and an extracellular loop which folds back to form the pore-lining ion selectivity filter. In vivo, functional Kir channels are composed of four such subunits which are either homo- or heterotetramers. Gene targeting and genetic analysis have linked Kir channel dysfunction to diverse pathologies. The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.
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              Purinergic signaling and blood vessels in health and disease.

              Purinergic signaling plays important roles in control of vascular tone and remodeling. There is dual control of vascular tone by ATP released as a cotransmitter with noradrenaline from perivascular sympathetic nerves to cause vasoconstriction via P2X1 receptors, whereas ATP released from endothelial cells in response to changes in blood flow (producing shear stress) or hypoxia acts on P2X and P2Y receptors on endothelial cells to produce nitric oxide and endothelium-derived hyperpolarizing factor, which dilates vessels. ATP is also released from sensory-motor nerves during antidromic reflex activity to produce relaxation of some blood vessels. In this review, we stress the differences in neural and endothelial factors in purinergic control of different blood vessels. The long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides in promoting migration and proliferation of both vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis and vessel remodeling during restenosis after angioplasty are described. The pathophysiology of blood vessels and therapeutic potential of purinergic agents in diseases, including hypertension, atherosclerosis, ischemia, thrombosis and stroke, diabetes, and migraine, is discussed.
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                Author and article information

                Contributors
                shiina.takahiko.a0@f.gifu-u.ac.jp
                Journal
                J Physiol Sci
                J Physiol Sci
                The Journal of Physiological Sciences : JPS
                BioMed Central (London )
                1880-6546
                1880-6562
                23 April 2024
                23 April 2024
                2024
                : 74
                : 26
                Affiliations
                [1 ]Department of Basic Veterinary Science, Laboratory of Physiology, Joint Graduate School of Veterinary Sciences, Gifu University, ( https://ror.org/024exxj48) 1-1 Yanagido, Gifu, 501-1193 Japan
                [2 ]Department of Basic Veterinary Science, Laboratory of Physiology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, ( https://ror.org/024exxj48) 1-1 Yanagido, Gifu, 501-1193 Japan
                [3 ]Division of Biological Principles, Department of Physiology, Graduate School of Medicine, Gifu University, ( https://ror.org/024exxj48) 1-1 Yanagido, Gifu, 501-1193 Japan
                [4 ]Institute for Glyco-Core Research (iGCORE), Gifu University, ( https://ror.org/024exxj48) 1-1 Yanagido, Gifu, 501-1193 Japan
                [5 ]Division of Animal Medical Science, Center for One Medicine Innovative Translational Research (COMIT), Gifu University Institute for Advanced Study, ( https://ror.org/024exxj48) 1-1 Yanagido, Gifu, 501-1193 Japan
                Author information
                http://orcid.org/0000-0002-3425-950X
                Article
                916
                10.1186/s12576-024-00916-5
                11036717
                38654149
                d25449da-6ac8-43b5-89b3-c98c33a17ca7
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 19 September 2023
                : 20 March 2024
                Funding
                Funded by: Grants-in-Aid for Scientific Research (KAKENHI)
                Award ID: 23K05553
                Award ID: 23H00360
                Award Recipient :
                Categories
                Original Paper
                Custom metadata
                © The Physiological Society of Japan 2024

                Anatomy & Physiology
                atp-dependent potassium channel,esophagus,p2 receptor,purine,smooth muscle
                Anatomy & Physiology
                atp-dependent potassium channel, esophagus, p2 receptor, purine, smooth muscle

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