Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations
Objectives Antimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lowe...
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| Veröffentlicht in: | Neurourology and urodynamics 2023-06, Vol.42 (5), p.1080-1087 |
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| creator | Veer, Vineesha Chess‐Williams, Russ Moro, Christian |
| description | Objectives
Antimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue.
Methods
Strips of porcine detrusor and U&LP were mounted in carbogen‐gassed Krebs‐bicarbonate solution at 37°C. The tissues were paired with carbachol‐response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated.
Results
Both detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p |
| doi_str_mv | 10.1002/nau.25176 |
| format | Article |
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Antimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue.
Methods
Strips of porcine detrusor and U&LP were mounted in carbogen‐gassed Krebs‐bicarbonate solution at 37°C. The tissues were paired with carbachol‐response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated.
Results
Both detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p < 0.001 for all), right parallel shifts from the control were observed in response to oxybutynin (1 µM), solifenacin (1 µM), tolterodine (1 µM), darifenacin (100 nM), trospium (100 nM) and fesoterodine (100 nM). This shift was consistent in U&LP samples, with no significant differences between the two layers.
Conclusions
The data suggests that clinical antimuscarinics are as effective at inhibiting tonic contractions of the U&LP as they are on detrusor, presenting the U&LP as an alternate target of these medications in the treatment of lower urinary tract symptoms.]]></description><identifier>ISSN: 0733-2467</identifier><identifier>EISSN: 1520-6777</identifier><identifier>DOI: 10.1002/nau.25176</identifier><identifier>PMID: 36975140</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acetylcholine receptors (muscarinic) ; Animals ; Bicarbonates ; Bladder ; Carbachol ; detrusor ; Lamina propria ; Mucous Membrane ; muscarinic antagonists ; Muscarinic Antagonists - pharmacology ; Muscarinic Antagonists - therapeutic use ; Muscle Contraction ; Muscle, Smooth ; overactive bladder ; Receptors, Muscarinic ; Smooth muscle ; Swine ; therapeutic targets ; Urinary Bladder ; Urinary Bladder, Overactive - drug therapy ; Urinary tract ; Urogenital system ; Urothelium</subject><ispartof>Neurourology and urodynamics, 2023-06, Vol.42 (5), p.1080-1087</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC.</rights><rights>2023 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-905015cc9bfd0e1a609cad80281e3ce4a235862817c167b5a13522f10883e2b03</citedby><cites>FETCH-LOGICAL-c3886-905015cc9bfd0e1a609cad80281e3ce4a235862817c167b5a13522f10883e2b03</cites><orcidid>0000-0002-7991-4117 ; 0000-0002-0933-1952 ; 0000-0003-2190-8301</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fnau.25176$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnau.25176$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36975140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veer, Vineesha</creatorcontrib><creatorcontrib>Chess‐Williams, Russ</creatorcontrib><creatorcontrib>Moro, Christian</creatorcontrib><title>Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations</title><title>Neurourology and urodynamics</title><addtitle>Neurourol Urodyn</addtitle><description><![CDATA[Objectives
Antimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue.
Methods
Strips of porcine detrusor and U&LP were mounted in carbogen‐gassed Krebs‐bicarbonate solution at 37°C. The tissues were paired with carbachol‐response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated.
Results
Both detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p < 0.001 for all), right parallel shifts from the control were observed in response to oxybutynin (1 µM), solifenacin (1 µM), tolterodine (1 µM), darifenacin (100 nM), trospium (100 nM) and fesoterodine (100 nM). This shift was consistent in U&LP samples, with no significant differences between the two layers.
Conclusions
The data suggests that clinical antimuscarinics are as effective at inhibiting tonic contractions of the U&LP as they are on detrusor, presenting the U&LP as an alternate target of these medications in the treatment of lower urinary tract symptoms.]]></description><subject>Acetylcholine receptors (muscarinic)</subject><subject>Animals</subject><subject>Bicarbonates</subject><subject>Bladder</subject><subject>Carbachol</subject><subject>detrusor</subject><subject>Lamina propria</subject><subject>Mucous Membrane</subject><subject>muscarinic antagonists</subject><subject>Muscarinic Antagonists - pharmacology</subject><subject>Muscarinic Antagonists - therapeutic use</subject><subject>Muscle Contraction</subject><subject>Muscle, Smooth</subject><subject>overactive bladder</subject><subject>Receptors, Muscarinic</subject><subject>Smooth muscle</subject><subject>Swine</subject><subject>therapeutic targets</subject><subject>Urinary Bladder</subject><subject>Urinary Bladder, Overactive - drug therapy</subject><subject>Urinary tract</subject><subject>Urogenital system</subject><subject>Urothelium</subject><issn>0733-2467</issn><issn>1520-6777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kc1u1DAURi0EokNhwQsgS2xgkfbaTmJnOar4kyrY0HV049xRXTn2YMegPgZvjGemZYHE6srS8fH19zH2WsCFAJCXAcuF7ITun7CN6CQ0vdb6KduAVqqRba_P2Iuc7wDAqHZ4zs5UP-hOtLBhv7dhdUvJFpMLznK0q4sh8xj45HGeKfGS4npL3pWFY5i5x8UF5PsU98khtzGs6fEWJuLZLc5j4mvk623MxOOUKf2kmbvAZ1pTyTHxvMRq5YeXPVUZ7THhUfKSPduhz_TqYZ6zm48fvl99bq6_ffpytb1urDKmbwboQHTWDtNuBhLYw2BxNiCNIGWpRak609eTtqLXU4dCdVLuBBijSE6gztm7k7f-5EehvI6Ly5a8x0Cx5FEaabRuWyMr-vYf9C6WFOp2R6pGL9sD9f5E2RRzTrQba0ALpvtRwHjoaaw9jceeKvvmwVimhea_5GMxFbg8Ab-cp_v_m8av25uT8g_zep7a</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Veer, Vineesha</creator><creator>Chess‐Williams, Russ</creator><creator>Moro, Christian</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7991-4117</orcidid><orcidid>https://orcid.org/0000-0002-0933-1952</orcidid><orcidid>https://orcid.org/0000-0003-2190-8301</orcidid></search><sort><creationdate>202306</creationdate><title>Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations</title><author>Veer, Vineesha ; Chess‐Williams, Russ ; Moro, Christian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-905015cc9bfd0e1a609cad80281e3ce4a235862817c167b5a13522f10883e2b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acetylcholine receptors (muscarinic)</topic><topic>Animals</topic><topic>Bicarbonates</topic><topic>Bladder</topic><topic>Carbachol</topic><topic>detrusor</topic><topic>Lamina propria</topic><topic>Mucous Membrane</topic><topic>muscarinic antagonists</topic><topic>Muscarinic Antagonists - pharmacology</topic><topic>Muscarinic Antagonists - therapeutic use</topic><topic>Muscle Contraction</topic><topic>Muscle, Smooth</topic><topic>overactive bladder</topic><topic>Receptors, Muscarinic</topic><topic>Smooth muscle</topic><topic>Swine</topic><topic>therapeutic targets</topic><topic>Urinary Bladder</topic><topic>Urinary Bladder, Overactive - drug therapy</topic><topic>Urinary tract</topic><topic>Urogenital system</topic><topic>Urothelium</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Veer, Vineesha</creatorcontrib><creatorcontrib>Chess‐Williams, Russ</creatorcontrib><creatorcontrib>Moro, Christian</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Neurourology and urodynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Veer, Vineesha</au><au>Chess‐Williams, Russ</au><au>Moro, Christian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations</atitle><jtitle>Neurourology and urodynamics</jtitle><addtitle>Neurourol Urodyn</addtitle><date>2023-06</date><risdate>2023</risdate><volume>42</volume><issue>5</issue><spage>1080</spage><epage>1087</epage><pages>1080-1087</pages><issn>0733-2467</issn><eissn>1520-6777</eissn><abstract><![CDATA[Objectives
Antimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue.
Methods
Strips of porcine detrusor and U&LP were mounted in carbogen‐gassed Krebs‐bicarbonate solution at 37°C. The tissues were paired with carbachol‐response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated.
Results
Both detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p < 0.001 for all), right parallel shifts from the control were observed in response to oxybutynin (1 µM), solifenacin (1 µM), tolterodine (1 µM), darifenacin (100 nM), trospium (100 nM) and fesoterodine (100 nM). This shift was consistent in U&LP samples, with no significant differences between the two layers.
Conclusions
The data suggests that clinical antimuscarinics are as effective at inhibiting tonic contractions of the U&LP as they are on detrusor, presenting the U&LP as an alternate target of these medications in the treatment of lower urinary tract symptoms.]]></abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36975140</pmid><doi>10.1002/nau.25176</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7991-4117</orcidid><orcidid>https://orcid.org/0000-0002-0933-1952</orcidid><orcidid>https://orcid.org/0000-0003-2190-8301</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcholine receptors (muscarinic) Animals Bicarbonates Bladder Carbachol detrusor Lamina propria Mucous Membrane muscarinic antagonists Muscarinic Antagonists - pharmacology Muscarinic Antagonists - therapeutic use Muscle Contraction Muscle, Smooth overactive bladder Receptors, Muscarinic Smooth muscle Swine therapeutic targets Urinary Bladder Urinary Bladder, Overactive - drug therapy Urinary tract Urogenital system Urothelium |
| title | Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations |
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