Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis
Objective To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis. Material and Methods TRPV4 expression in bladder afferents w...
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| Veröffentlicht in: | BJU international 2015-03, Vol.115 (3), p.452-460 |
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| creator | Charrua, Ana Cruz, Célia D. Jansen, Dick Rozenberg, Boy Heesakkers, John Cruz, Francisco |
| description | Objective
To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis.
Material and Methods
TRPV4 expression in bladder afferents was analysed by immunohistochemistry in L6 dorsal root ganglia (DRG), labelled by fluorogold injected in the urinary bladder. TRPV4 and TRPV1 co‐expression was also investigated in L6 DRG neurones of control rats and in rats with lipopolysaccharide (LPS)‐induced cystitis. The effect of TRPV4 antagonist RN1734 and TRPV1 antagonist SB366791 on bladder hyperactivity and pain induced by cystitis was assessed by cystometry and visceral pain behaviour tests, respectively.
Results
TRPV4 is expressed in sensory neurones that innervate the urinary bladder. TRPV4‐positive bladder afferents represent a different population than the TRPV1‐expressing bladder afferents, as their co‐localisation was minimal in control and inflamed rats. While low doses of RN1734 and SB366791 (176.7 ng/kg and 143.9 ng/kg, respectively) had no effect on bladder activity, the co‐administration of the two totally reversed bladder hyperactivity induced by LPS. In these same doses, the antagonists partially reversed bladder pain behaviour induced by cystitis.
Conclusions
TRPV4 and TRPV1 are present in different bladder afferent populations. The synergistic activity of antagonists for these receptors in very low doses may offer the opportunity to treat lower urinary tract symptoms while minimising the potential side‐effects of each drug. |
| doi_str_mv | 10.1111/bju.12861 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1891867734</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1891867734</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5221-218632fb515ee8e452940dd311fb4802223b4947685a5e76b0798a433f0a25f43</originalsourceid><addsrcrecordid>eNqNkc1uFSEYhidGY3904Q0YEjft4rR8DDDMUk-stmmiMa1xN2FmPlpOZuAIjM3Z9RLce3deiUxP24WJiWx4gYeHkLcoXgE9gjyO29V0BExJeFLsApd8wYF-e_qQaS13ir0YV5TmDSmeFztMUA5Ql7vFr6X_fftT96N1Nqagk_WOeENydNGiSyRgh-vkA1n7lNdWD-SHdnYYvO0JJwcXXz5_5YdEu57MEXJK-srPuvh4JyFJ10jQGOzS7EfdXZM-TFfEOqJJfpiMvsdhPus2Mdlk44vimdFDxJf3835xefL-Yvlxcf7pw-ny7fmiE4zBgoGSJTOtAIGokAtWc9r3JYBpuaKMsbLlNa-kElpgJVta1UrzsjRUM2F4uV8cbL3r4L9PGFMz2tjhMGiHfooNqDo_UVXlf6BSiIpJxVRG3_yFrvwUXP7IHcWA1goydbiluuBjDGiadbCjDpsGaDOX2-Rym7tyM_v63ji1I_aP5EObGTjeAjd2wM2_Tc27s8ut8g-Fqq2a</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1655210981</pqid></control><display><type>article</type><title>Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis</title><source>MEDLINE</source><source>Wiley Journals</source><creator>Charrua, Ana ; Cruz, Célia D. ; Jansen, Dick ; Rozenberg, Boy ; Heesakkers, John ; Cruz, Francisco</creator><creatorcontrib>Charrua, Ana ; Cruz, Célia D. ; Jansen, Dick ; Rozenberg, Boy ; Heesakkers, John ; Cruz, Francisco</creatorcontrib><description>Objective
To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis.
Material and Methods
TRPV4 expression in bladder afferents was analysed by immunohistochemistry in L6 dorsal root ganglia (DRG), labelled by fluorogold injected in the urinary bladder. TRPV4 and TRPV1 co‐expression was also investigated in L6 DRG neurones of control rats and in rats with lipopolysaccharide (LPS)‐induced cystitis. The effect of TRPV4 antagonist RN1734 and TRPV1 antagonist SB366791 on bladder hyperactivity and pain induced by cystitis was assessed by cystometry and visceral pain behaviour tests, respectively.
Results
TRPV4 is expressed in sensory neurones that innervate the urinary bladder. TRPV4‐positive bladder afferents represent a different population than the TRPV1‐expressing bladder afferents, as their co‐localisation was minimal in control and inflamed rats. While low doses of RN1734 and SB366791 (176.7 ng/kg and 143.9 ng/kg, respectively) had no effect on bladder activity, the co‐administration of the two totally reversed bladder hyperactivity induced by LPS. In these same doses, the antagonists partially reversed bladder pain behaviour induced by cystitis.
Conclusions
TRPV4 and TRPV1 are present in different bladder afferent populations. The synergistic activity of antagonists for these receptors in very low doses may offer the opportunity to treat lower urinary tract symptoms while minimising the potential side‐effects of each drug.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/bju.12861</identifier><identifier>PMID: 25041193</identifier><identifier>CODEN: BJINFO</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Anilides - pharmacology ; Animals ; Behavior, Animal - drug effects ; Bladder ; Cinnamates - pharmacology ; cystitis ; Cystitis - drug therapy ; Cystitis - metabolism ; Disease Models, Animal ; Drug Discovery ; Drug dosages ; Female ; Ganglia, Spinal - chemistry ; Hyperactivity ; lower urinary tract ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Pain Measurement ; Rats ; Rats, Wistar ; Rodents ; Studies ; Sulfonamides - pharmacology ; TRPV Cation Channels - antagonists & inhibitors ; TRPV Cation Channels - metabolism ; TRPV1 antagonist ; TRPV4 antagonist ; Urinary Bladder - drug effects</subject><ispartof>BJU international, 2015-03, Vol.115 (3), p.452-460</ispartof><rights>2014 The Authors. BJU International © 2014 BJU International</rights><rights>2014 The Authors. BJU International © 2014 BJU International.</rights><rights>BJUI © 2015 BJU International</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5221-218632fb515ee8e452940dd311fb4802223b4947685a5e76b0798a433f0a25f43</citedby><cites>FETCH-LOGICAL-c5221-218632fb515ee8e452940dd311fb4802223b4947685a5e76b0798a433f0a25f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbju.12861$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbju.12861$$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/25041193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Charrua, Ana</creatorcontrib><creatorcontrib>Cruz, Célia D.</creatorcontrib><creatorcontrib>Jansen, Dick</creatorcontrib><creatorcontrib>Rozenberg, Boy</creatorcontrib><creatorcontrib>Heesakkers, John</creatorcontrib><creatorcontrib>Cruz, Francisco</creatorcontrib><title>Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>Objective
To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis.
Material and Methods
TRPV4 expression in bladder afferents was analysed by immunohistochemistry in L6 dorsal root ganglia (DRG), labelled by fluorogold injected in the urinary bladder. TRPV4 and TRPV1 co‐expression was also investigated in L6 DRG neurones of control rats and in rats with lipopolysaccharide (LPS)‐induced cystitis. The effect of TRPV4 antagonist RN1734 and TRPV1 antagonist SB366791 on bladder hyperactivity and pain induced by cystitis was assessed by cystometry and visceral pain behaviour tests, respectively.
Results
TRPV4 is expressed in sensory neurones that innervate the urinary bladder. TRPV4‐positive bladder afferents represent a different population than the TRPV1‐expressing bladder afferents, as their co‐localisation was minimal in control and inflamed rats. While low doses of RN1734 and SB366791 (176.7 ng/kg and 143.9 ng/kg, respectively) had no effect on bladder activity, the co‐administration of the two totally reversed bladder hyperactivity induced by LPS. In these same doses, the antagonists partially reversed bladder pain behaviour induced by cystitis.
Conclusions
TRPV4 and TRPV1 are present in different bladder afferent populations. The synergistic activity of antagonists for these receptors in very low doses may offer the opportunity to treat lower urinary tract symptoms while minimising the potential side‐effects of each drug.</description><subject>Anilides - pharmacology</subject><subject>Animals</subject><subject>Behavior, Animal - drug effects</subject><subject>Bladder</subject><subject>Cinnamates - pharmacology</subject><subject>cystitis</subject><subject>Cystitis - drug therapy</subject><subject>Cystitis - metabolism</subject><subject>Disease Models, Animal</subject><subject>Drug Discovery</subject><subject>Drug dosages</subject><subject>Female</subject><subject>Ganglia, Spinal - chemistry</subject><subject>Hyperactivity</subject><subject>lower urinary tract</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Pain Measurement</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Rodents</subject><subject>Studies</subject><subject>Sulfonamides - pharmacology</subject><subject>TRPV Cation Channels - antagonists & inhibitors</subject><subject>TRPV Cation Channels - metabolism</subject><subject>TRPV1 antagonist</subject><subject>TRPV4 antagonist</subject><subject>Urinary Bladder - drug effects</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1uFSEYhidGY3904Q0YEjft4rR8DDDMUk-stmmiMa1xN2FmPlpOZuAIjM3Z9RLce3deiUxP24WJiWx4gYeHkLcoXgE9gjyO29V0BExJeFLsApd8wYF-e_qQaS13ir0YV5TmDSmeFztMUA5Ql7vFr6X_fftT96N1Nqagk_WOeENydNGiSyRgh-vkA1n7lNdWD-SHdnYYvO0JJwcXXz5_5YdEu57MEXJK-srPuvh4JyFJ10jQGOzS7EfdXZM-TFfEOqJJfpiMvsdhPus2Mdlk44vimdFDxJf3835xefL-Yvlxcf7pw-ny7fmiE4zBgoGSJTOtAIGokAtWc9r3JYBpuaKMsbLlNa-kElpgJVta1UrzsjRUM2F4uV8cbL3r4L9PGFMz2tjhMGiHfooNqDo_UVXlf6BSiIpJxVRG3_yFrvwUXP7IHcWA1goydbiluuBjDGiadbCjDpsGaDOX2-Rym7tyM_v63ji1I_aP5EObGTjeAjd2wM2_Tc27s8ut8g-Fqq2a</recordid><startdate>201503</startdate><enddate>201503</enddate><creator>Charrua, Ana</creator><creator>Cruz, Célia D.</creator><creator>Jansen, Dick</creator><creator>Rozenberg, Boy</creator><creator>Heesakkers, John</creator><creator>Cruz, Francisco</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7X8</scope></search><sort><creationdate>201503</creationdate><title>Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis</title><author>Charrua, Ana ; Cruz, Célia D. ; Jansen, Dick ; Rozenberg, Boy ; Heesakkers, John ; Cruz, Francisco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5221-218632fb515ee8e452940dd311fb4802223b4947685a5e76b0798a433f0a25f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anilides - pharmacology</topic><topic>Animals</topic><topic>Behavior, Animal - drug effects</topic><topic>Bladder</topic><topic>Cinnamates - pharmacology</topic><topic>cystitis</topic><topic>Cystitis - drug therapy</topic><topic>Cystitis - metabolism</topic><topic>Disease Models, Animal</topic><topic>Drug Discovery</topic><topic>Drug dosages</topic><topic>Female</topic><topic>Ganglia, Spinal - chemistry</topic><topic>Hyperactivity</topic><topic>lower urinary tract</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Pain Measurement</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Rodents</topic><topic>Studies</topic><topic>Sulfonamides - pharmacology</topic><topic>TRPV Cation Channels - antagonists & inhibitors</topic><topic>TRPV Cation Channels - metabolism</topic><topic>TRPV1 antagonist</topic><topic>TRPV4 antagonist</topic><topic>Urinary Bladder - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Charrua, Ana</creatorcontrib><creatorcontrib>Cruz, Célia D.</creatorcontrib><creatorcontrib>Jansen, Dick</creatorcontrib><creatorcontrib>Rozenberg, Boy</creatorcontrib><creatorcontrib>Heesakkers, John</creatorcontrib><creatorcontrib>Cruz, Francisco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Charrua, Ana</au><au>Cruz, Célia D.</au><au>Jansen, Dick</au><au>Rozenberg, Boy</au><au>Heesakkers, John</au><au>Cruz, Francisco</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2015-03</date><risdate>2015</risdate><volume>115</volume><issue>3</issue><spage>452</spage><epage>460</epage><pages>452-460</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><coden>BJINFO</coden><abstract>Objective
To investigate transient receptor potential vanilloid 4 (TRPV4) expression in bladder afferents and study the effect of TRPV4 and TRPV1 antagonists, alone and in combination, in bladder hyperactivity and pain induced by cystitis.
Material and Methods
TRPV4 expression in bladder afferents was analysed by immunohistochemistry in L6 dorsal root ganglia (DRG), labelled by fluorogold injected in the urinary bladder. TRPV4 and TRPV1 co‐expression was also investigated in L6 DRG neurones of control rats and in rats with lipopolysaccharide (LPS)‐induced cystitis. The effect of TRPV4 antagonist RN1734 and TRPV1 antagonist SB366791 on bladder hyperactivity and pain induced by cystitis was assessed by cystometry and visceral pain behaviour tests, respectively.
Results
TRPV4 is expressed in sensory neurones that innervate the urinary bladder. TRPV4‐positive bladder afferents represent a different population than the TRPV1‐expressing bladder afferents, as their co‐localisation was minimal in control and inflamed rats. While low doses of RN1734 and SB366791 (176.7 ng/kg and 143.9 ng/kg, respectively) had no effect on bladder activity, the co‐administration of the two totally reversed bladder hyperactivity induced by LPS. In these same doses, the antagonists partially reversed bladder pain behaviour induced by cystitis.
Conclusions
TRPV4 and TRPV1 are present in different bladder afferent populations. The synergistic activity of antagonists for these receptors in very low doses may offer the opportunity to treat lower urinary tract symptoms while minimising the potential side‐effects of each drug.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25041193</pmid><doi>10.1111/bju.12861</doi><tpages>9</tpages></addata></record> |
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| identifier | ISSN: 1464-4096 |
| ispartof | BJU international, 2015-03, Vol.115 (3), p.452-460 |
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| source | MEDLINE; Wiley Journals |
| subjects | Anilides - pharmacology Animals Behavior, Animal - drug effects Bladder Cinnamates - pharmacology cystitis Cystitis - drug therapy Cystitis - metabolism Disease Models, Animal Drug Discovery Drug dosages Female Ganglia, Spinal - chemistry Hyperactivity lower urinary tract Mice Mice, Knockout Molecular Sequence Data Pain Measurement Rats Rats, Wistar Rodents Studies Sulfonamides - pharmacology TRPV Cation Channels - antagonists & inhibitors TRPV Cation Channels - metabolism TRPV1 antagonist TRPV4 antagonist Urinary Bladder - drug effects |
| title | Co‐administration of transient receptor potential vanilloid 4 (TRPV4) and TRPV1 antagonists potentiate the effect of each drug in a rat model of cystitis |
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