LBA01-04 NERVE TRANSFER FOR RESTORATION OF LOWER MOTOR NEURON-LESIONED BLADDER, URETHRAL AND ANAL SPHINCTER FUNCTION IN A DOG MODEL. PART 3: NEUROPHARMACOLOGICAL CHARACTERIZATION OF NICOTINIC RECEPTORS IN VITRO

Abstract

You have accessJournal of UrologyCME1 Apr 2023LBA01-04 NERVE TRANSFER FOR RESTORATION OF LOWER MOTOR NEURON-LESIONED BLADDER, URETHRAL AND ANAL SPHINCTER FUNCTION IN A DOG MODEL. PART 3: NEUROPHARMACOLOGICAL CHARACTERIZATION OF NICOTINIC RECEPTORS IN VITRO Nagat Frara, Dania Giaddui, Danielle S. Porreca, Alan S. Braverman, Ekta Tiwari, Attia Ahmad, Justin M. Brown, Benjamin R. Johnston, Stanley F. Bazarek, Michael R. Ruggieri Sr, and Mary F. Barbe Nagat FraraNagat Frara More articles by this author , Dania GiadduiDania Giaddui More articles by this author , Danielle S. PorrecaDanielle S. Porreca More articles by this author , Alan S. BravermanAlan S. Braverman More articles by this author , Ekta TiwariEkta Tiwari More articles by this author , Attia AhmadAttia Ahmad More articles by this author , Justin M. BrownJustin M. Brown More articles by this author , Benjamin R. JohnstonBenjamin R. Johnston More articles by this author , Stanley F. BazarekStanley F. Bazarek More articles by this author , Michael R. Ruggieri SrMichael R. Ruggieri Sr More articles by this author , and Mary F. BarbeMary F. Barbe More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003360.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Utilizing in vitro contractility and pharmacological methods, we evaluated responses of cholinergic nicotinic receptor subtypes, mediating bladder muscle function, to selected receptor agonists and antagonists, in control dogs, and how those receptors were altered after bladder decentralization, and bladder decentralization and then reinnervation. METHODS: Bladder tissues were obtained from 43 male and female dogs, divided into 4 groups: normal controls (9 females, 11 males), sham-operated controls (5 females), decentralized (9 females, decentralized 6-21 mo), and obturator-to-pelvic nerve transfer reinnervated (ObNT-Reinn, 9 females, decentralized 9-13 mo, reinnervated, 8-12 mo recovery). Mucosa free smooth muscle strips were collected and mounted in muscle baths before incubation with cholinergic receptor subtype antagonists (20 min), and contractions to epibatidine (nicotinic receptor agonist) determined. RESULTS: Male and female control bladder strips had similar responses to potassium chloride (KCl) and epibatidine. The average strip response to epibatidine (measured as percentage of KCl response) was about 36% in Control, 32% in Decentralized, and 24% in ObNT-Reinn bladders, yet was not statistically significantly different across groups. Epibatidine-induced contractions in Control bladder strips were inhibited by atropine (muscarinic receptor antagonist), atracurium and tubocurarine (neuromuscular nicotinic receptor antagonists), mecamylamine and hexamethonium (ganglionic nicotinic receptor antagonists), and SR 16584 (α3β4 neuronal nicotinic receptor subtype specific antagonist), compared to vehicle treatment. Differentially, epibatidine responses in Decentralized and ObNT-Reinn bladder strips were lower than Controls after tetrodotoxin (TTX, a sodium channel blocker), although not after atracurium. Hexamethonium cased more blockade of strip contractions in ObNT-Reinn bladders, compared to Controls. CONCLUSIONS: Since TTX did not block epibatidine contraction in Control bladders, nicotinic receptors are likely located on nerve terminals. In Decentralized and ObNT-Reinn bladders, TTX blockade suggests a relocation of receptors from nerve terminals to along axons distant from the neuromuscular junction. The possible change in nicotinic receptors profile after decentralization suggests a physiological relevance for these receptors as a compensatory mechanism to recover bladder function, and a potential target for drug treatment. Source of Funding: NINDS R01NS070267 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1177 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nagat Frara More articles by this author Dania Giaddui More articles by this author Danielle S. Porreca More articles by this author Alan S. Braverman More articles by this author Ekta Tiwari More articles by this author Attia Ahmad More articles by this author Justin M. Brown More articles by this author Benjamin R. Johnston More articles by this author Stanley F. Bazarek More articles by this author Michael R. Ruggieri Sr More articles by this author Mary F. Barbe More articles by this author Expand All Advertisement PDF downloadLoading ...