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In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder.
Auton Neurosci. 2020 09; 227:102689.AN

Abstract

Mechanical stretch of the urothelium induces the release of ATP that activates bladder afferent nerves. In the rat urinary bladder, ATP is also a contractile co-transmitter in the parasympathetic innervation. In isolated preparations, ATP evokes a urothelial release of acetylcholine that substantially contributes to ATP-evoked contractile responses. Currently we aimed to further examine the interactions of ATP and acetylcholine in the rat urinary bladder in two in vivo models. In the whole bladder preparation, atropine reduced ATP-evoked responses by about 50% in intact but denervated bladders, while atropine had no effect after denudation of the urothelium. In a split bladder preparation, reflex-evoked responses of the contralateral half were studied by applying stimuli (agonists or stretch) to the ipsilateral half. Topical administration of ATP and methacholine as well as of stretch induced contralateral reflex-evoked contractions. While topical administration of atropine ipsilaterally reduced the ATP- and stretch-induced contralateral contractions by 27 and 39%, respectively, the P2X purinoceptor antagonist PPADS reduced them by 74 and 84%. In contrary, the muscarinic M2-(M4)-selective receptor antagonist methoctramine increased the responses by 38% (ATP) and 75% (stretch). Pirenzepine (M1-selective antagonist) had no effect on the reflex. In vitro, in the absence of the reflex, methoctramine did not affect the ATP-induced responses. It is concluded that urothelial ATP potently induces the micturition reflex and stimulates urothelial release of acetylcholine. Acetylcholine subsequently acts on afferents and on the detrusor muscle. While muscarinic M2 and/or M4 receptors in the sensory innervation exert inhibitory modulation, muscarinic M3 receptors cause excitation.

Authors+Show Affiliations

Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 431, 405 30 Gothenburg, Sweden.Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 431, 405 30 Gothenburg, Sweden.Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 431, 405 30 Gothenburg, Sweden.Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 431, 405 30 Gothenburg, Sweden.Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Box 431, 405 30 Gothenburg, Sweden. Electronic address: gunnar.tobin@pharm.gu.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32473532

Citation

Stenqvist, Johanna, et al. "In Vivo Paracrine Effects of ATP-induced Urothelial Acetylcholine in the Rat Urinary Bladder." Autonomic Neuroscience : Basic & Clinical, vol. 227, 2020, p. 102689.
Stenqvist J, Aronsson P, Carlsson T, et al. In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder. Auton Neurosci. 2020;227:102689.
Stenqvist, J., Aronsson, P., Carlsson, T., Winder, M., & Tobin, G. (2020). In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder. Autonomic Neuroscience : Basic & Clinical, 227, 102689. https://doi.org/10.1016/j.autneu.2020.102689
Stenqvist J, et al. In Vivo Paracrine Effects of ATP-induced Urothelial Acetylcholine in the Rat Urinary Bladder. Auton Neurosci. 2020;227:102689. PubMed PMID: 32473532.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo paracrine effects of ATP-induced urothelial acetylcholine in the rat urinary bladder. AU - Stenqvist,Johanna, AU - Aronsson,Patrik, AU - Carlsson,Thomas, AU - Winder,Michael, AU - Tobin,Gunnar, Y1 - 2020/05/23/ PY - 2020/03/16/received PY - 2020/05/13/revised PY - 2020/05/20/accepted PY - 2020/5/31/pubmed PY - 2020/5/31/medline PY - 2020/5/31/entrez KW - Afferens KW - Micturition reflex KW - Muscarinic modulation KW - Stretch KW - Topical administration SP - 102689 EP - 102689 JF - Autonomic neuroscience : basic & clinical JO - Auton Neurosci VL - 227 N2 - Mechanical stretch of the urothelium induces the release of ATP that activates bladder afferent nerves. In the rat urinary bladder, ATP is also a contractile co-transmitter in the parasympathetic innervation. In isolated preparations, ATP evokes a urothelial release of acetylcholine that substantially contributes to ATP-evoked contractile responses. Currently we aimed to further examine the interactions of ATP and acetylcholine in the rat urinary bladder in two in vivo models. In the whole bladder preparation, atropine reduced ATP-evoked responses by about 50% in intact but denervated bladders, while atropine had no effect after denudation of the urothelium. In a split bladder preparation, reflex-evoked responses of the contralateral half were studied by applying stimuli (agonists or stretch) to the ipsilateral half. Topical administration of ATP and methacholine as well as of stretch induced contralateral reflex-evoked contractions. While topical administration of atropine ipsilaterally reduced the ATP- and stretch-induced contralateral contractions by 27 and 39%, respectively, the P2X purinoceptor antagonist PPADS reduced them by 74 and 84%. In contrary, the muscarinic M2-(M4)-selective receptor antagonist methoctramine increased the responses by 38% (ATP) and 75% (stretch). Pirenzepine (M1-selective antagonist) had no effect on the reflex. In vitro, in the absence of the reflex, methoctramine did not affect the ATP-induced responses. It is concluded that urothelial ATP potently induces the micturition reflex and stimulates urothelial release of acetylcholine. Acetylcholine subsequently acts on afferents and on the detrusor muscle. While muscarinic M2 and/or M4 receptors in the sensory innervation exert inhibitory modulation, muscarinic M3 receptors cause excitation. SN - 1872-7484 UR - https://www.unboundmedicine.com/medline/citation/32473532/In_vivo_paracrine_effects_of_ATP-induced_urothelial_acetylcholine_in_the_rat_urinary_bladder L2 - https://linkinghub.elsevier.com/retrieve/pii/S1566-0702(20)30123-5 DB - PRIME DP - Unbound Medicine ER -
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