Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction

Aims Beta3‐adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3‐AR selective agonists exert their effects via a peripheral site of action. However, β3‐ARs have been found in brain tissue. This study examined whether...

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Veröffentlicht in:Neurourology and urodynamics 2011-09, Vol.30 (7), p.1382-1387
Hauptverfasser: Füllhase, Claudius, Soler, Roberto, Westerling-Andersson, Kristian, Andersson, Karl-Erik
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creator Füllhase, Claudius
Soler, Roberto
Westerling-Andersson, Kristian
Andersson, Karl-Erik
description Aims Beta3‐adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3‐AR selective agonists exert their effects via a peripheral site of action. However, β3‐ARs have been found in brain tissue. This study examined whether β3‐ARs are present in rat sacral spinal cord, and whether there are differences in β3‐AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3‐ARs for micturition. Methods Thirty‐eight male Sprague–Dawley rats underwent either PUO or sham‐operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3‐AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non‐anesthetized animals before and after drug administration. Results Beta3‐ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3‐AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P 
doi_str_mv 10.1002/nau.21071
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It is believed that β3‐AR selective agonists exert their effects via a peripheral site of action. However, β3‐ARs have been found in brain tissue. This study examined whether β3‐ARs are present in rat sacral spinal cord, and whether there are differences in β3‐AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3‐ARs for micturition. Methods Thirty‐eight male Sprague–Dawley rats underwent either PUO or sham‐operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3‐AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non‐anesthetized animals before and after drug administration. Results Beta3‐ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3‐AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P &lt; 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non‐obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P &lt; 0.05). Conclusions Beta3‐ARs are present in rat sacral spinal cord, and are significantly up‐regulated after PUO. Besides their well‐established peripheral site of action in the treatment of voiding dysfunction, β3‐AR selective agonists might exert relevant effects at a central nervous site of action. Neurourol. Urodynam. 30:1382–1387, 2011. © 2011 Wiley‐Liss, Inc.</description><identifier>ISSN: 0733-2467</identifier><identifier>EISSN: 1520-6777</identifier><identifier>DOI: 10.1002/nau.21071</identifier><identifier>PMID: 21661032</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Adrenergic beta-3 Receptor Agonists - administration &amp; dosage ; Animals ; benign prostatic hyperplasia ; beta3-adrenoreceptor agonist ; Blotting, Western ; cystometry ; Disease Models, Animal ; Ethanolamines - administration &amp; dosage ; Immunohistochemistry ; intrathecal ; Male ; overactive bladder ; Pilot Projects ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-3 - metabolism ; Sacrum ; Spinal Cord - drug effects ; Spinal Cord - metabolism ; Spinal Cord - physiopathology ; Time Factors ; Up-Regulation ; Urethral Obstruction - drug therapy ; Urethral Obstruction - metabolism ; Urethral Obstruction - physiopathology ; Urinary Bladder - innervation ; Urination - drug effects ; Urodynamics</subject><ispartof>Neurourology and urodynamics, 2011-09, Vol.30 (7), p.1382-1387</ispartof><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3621-f4e52fd10c389623f6a148d2a04ab4501dc88180df743db61ee08437ebc317093</citedby><cites>FETCH-LOGICAL-c3621-f4e52fd10c389623f6a148d2a04ab4501dc88180df743db61ee08437ebc317093</cites></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.21071$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fnau.21071$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21661032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Füllhase, Claudius</creatorcontrib><creatorcontrib>Soler, Roberto</creatorcontrib><creatorcontrib>Westerling-Andersson, Kristian</creatorcontrib><creatorcontrib>Andersson, Karl-Erik</creatorcontrib><title>Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction</title><title>Neurourology and urodynamics</title><addtitle>Neurourol. Urodyn</addtitle><description>Aims Beta3‐adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3‐AR selective agonists exert their effects via a peripheral site of action. However, β3‐ARs have been found in brain tissue. This study examined whether β3‐ARs are present in rat sacral spinal cord, and whether there are differences in β3‐AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3‐ARs for micturition. Methods Thirty‐eight male Sprague–Dawley rats underwent either PUO or sham‐operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3‐AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non‐anesthetized animals before and after drug administration. Results Beta3‐ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3‐AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P &lt; 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non‐obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P &lt; 0.05). Conclusions Beta3‐ARs are present in rat sacral spinal cord, and are significantly up‐regulated after PUO. Besides their well‐established peripheral site of action in the treatment of voiding dysfunction, β3‐AR selective agonists might exert relevant effects at a central nervous site of action. Neurourol. Urodynam. 30:1382–1387, 2011. © 2011 Wiley‐Liss, Inc.</description><subject>Adrenergic beta-3 Receptor Agonists - administration &amp; dosage</subject><subject>Animals</subject><subject>benign prostatic hyperplasia</subject><subject>beta3-adrenoreceptor agonist</subject><subject>Blotting, Western</subject><subject>cystometry</subject><subject>Disease Models, Animal</subject><subject>Ethanolamines - administration &amp; dosage</subject><subject>Immunohistochemistry</subject><subject>intrathecal</subject><subject>Male</subject><subject>overactive bladder</subject><subject>Pilot Projects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Adrenergic, beta-3 - metabolism</subject><subject>Sacrum</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - metabolism</subject><subject>Spinal Cord - physiopathology</subject><subject>Time Factors</subject><subject>Up-Regulation</subject><subject>Urethral Obstruction - drug therapy</subject><subject>Urethral Obstruction - metabolism</subject><subject>Urethral Obstruction - physiopathology</subject><subject>Urinary Bladder - innervation</subject><subject>Urination - drug effects</subject><subject>Urodynamics</subject><issn>0733-2467</issn><issn>1520-6777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1u1TAQhS0EopfCghdA3iEWaf2TxLnLtuq9IKoiARVLy7EnqiGxw9gB-kI8J0lu2x2rkeZ854w0h5DXnJ1wxsRpMNOJ4EzxJ2TDK8GKWin1lGyYkrIQZa2OyIuUvjPGGllun5MjweuaMyk25O85ZCML4xBCtDDmiIn6QPMtUDSZJmPR9DSNPszDRnTUBLfIHmk3BZt9XBSEHn6ZYGExD97mCf0i0Sk4QBoiDqs_uHWd1pQZNXSIDnoaOzoazH6GJoR8uxyNbco4rRdekmed6RO8up_H5GZ3-fXifXH1af_h4uyqsLIWvOhKqETnOLOy2dZCdrXhZeOEYaVpy4pxZ5uGN8x1qpSurTkAa0qpoLWSK7aVx-TtIXfE-HOClPXgk4W-NwHilHTTqIrJ-ecz-e5AWowpIXR6RD8YvNOc6aUVPbei11Zm9s196tQO4B7Jhxpm4PQA_PY93P0_SV-f3TxEFgeHTxn-PDoM_tC1kqrS3673mqvPu935l73-KP8BXlWovw</recordid><startdate>201109</startdate><enddate>201109</enddate><creator>Füllhase, Claudius</creator><creator>Soler, Roberto</creator><creator>Westerling-Andersson, Kristian</creator><creator>Andersson, Karl-Erik</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201109</creationdate><title>Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction</title><author>Füllhase, Claudius ; Soler, Roberto ; Westerling-Andersson, Kristian ; Andersson, Karl-Erik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3621-f4e52fd10c389623f6a148d2a04ab4501dc88180df743db61ee08437ebc317093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adrenergic beta-3 Receptor Agonists - administration &amp; dosage</topic><topic>Animals</topic><topic>benign prostatic hyperplasia</topic><topic>beta3-adrenoreceptor agonist</topic><topic>Blotting, Western</topic><topic>cystometry</topic><topic>Disease Models, Animal</topic><topic>Ethanolamines - administration &amp; dosage</topic><topic>Immunohistochemistry</topic><topic>intrathecal</topic><topic>Male</topic><topic>overactive bladder</topic><topic>Pilot Projects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Adrenergic, beta-3 - metabolism</topic><topic>Sacrum</topic><topic>Spinal Cord - drug effects</topic><topic>Spinal Cord - metabolism</topic><topic>Spinal Cord - physiopathology</topic><topic>Time Factors</topic><topic>Up-Regulation</topic><topic>Urethral Obstruction - drug therapy</topic><topic>Urethral Obstruction - metabolism</topic><topic>Urethral Obstruction - physiopathology</topic><topic>Urinary Bladder - innervation</topic><topic>Urination - drug effects</topic><topic>Urodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Füllhase, Claudius</creatorcontrib><creatorcontrib>Soler, Roberto</creatorcontrib><creatorcontrib>Westerling-Andersson, Kristian</creatorcontrib><creatorcontrib>Andersson, Karl-Erik</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Neurourology and urodynamics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Füllhase, Claudius</au><au>Soler, Roberto</au><au>Westerling-Andersson, Kristian</au><au>Andersson, Karl-Erik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction</atitle><jtitle>Neurourology and urodynamics</jtitle><addtitle>Neurourol. Urodyn</addtitle><date>2011-09</date><risdate>2011</risdate><volume>30</volume><issue>7</issue><spage>1382</spage><epage>1387</epage><pages>1382-1387</pages><issn>0733-2467</issn><eissn>1520-6777</eissn><abstract>Aims Beta3‐adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3‐AR selective agonists exert their effects via a peripheral site of action. However, β3‐ARs have been found in brain tissue. This study examined whether β3‐ARs are present in rat sacral spinal cord, and whether there are differences in β3‐AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3‐ARs for micturition. Methods Thirty‐eight male Sprague–Dawley rats underwent either PUO or sham‐operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3‐AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non‐anesthetized animals before and after drug administration. Results Beta3‐ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3‐AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P &lt; 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non‐obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P &lt; 0.05). Conclusions Beta3‐ARs are present in rat sacral spinal cord, and are significantly up‐regulated after PUO. Besides their well‐established peripheral site of action in the treatment of voiding dysfunction, β3‐AR selective agonists might exert relevant effects at a central nervous site of action. Neurourol. Urodynam. 30:1382–1387, 2011. © 2011 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21661032</pmid><doi>10.1002/nau.21071</doi><tpages>6</tpages></addata></record>
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subjects Adrenergic beta-3 Receptor Agonists - administration & dosage
Animals
benign prostatic hyperplasia
beta3-adrenoreceptor agonist
Blotting, Western
cystometry
Disease Models, Animal
Ethanolamines - administration & dosage
Immunohistochemistry
intrathecal
Male
overactive bladder
Pilot Projects
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta-3 - metabolism
Sacrum
Spinal Cord - drug effects
Spinal Cord - metabolism
Spinal Cord - physiopathology
Time Factors
Up-Regulation
Urethral Obstruction - drug therapy
Urethral Obstruction - metabolism
Urethral Obstruction - physiopathology
Urinary Bladder - innervation
Urination - drug effects
Urodynamics
title Beta3-adrenoceptors in the rat sacral spinal cord and their functional relevance in micturition under normal conditions and in a model of partial urethral obstruction
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