Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter

According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have perfor...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:PloS one 2014-11, Vol.9 (11), p.e113580
Hauptverfasser: Fernandes, Vítor S, Ribeiro, Ana S F, Martínez, Pilar, López-Oliva, María Elvira, Barahona, María Victoria, Orensanz, Luis M, Martínez-Sáenz, Ana, Recio, Paz, Benedito, Sara, Bustamante, Salvador, García-Sacristán, Albino, Prieto, Dolores, Hernández, Medardo
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 11
container_start_page e113580
container_title PloS one
container_volume 9
creator Fernandes, Vítor S
Ribeiro, Ana S F
Martínez, Pilar
López-Oliva, María Elvira
Barahona, María Victoria
Orensanz, Luis M
Martínez-Sáenz, Ana
Recio, Paz
Benedito, Sara
Bustamante, Salvador
García-Sacristán, Albino
Prieto, Dolores
Hernández, Medardo
description According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.
doi_str_mv 10.1371/journal.pone.0113580
format Article
fullrecord <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1626822671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418139025</galeid><doaj_id>oai_doaj_org_article_9f2943b83fb149c18ffa9e36fe941ec8</doaj_id><sourcerecordid>A418139025</sourcerecordid><originalsourceid>FETCH-LOGICAL-c762t-15585c337e6595167c9a04c5ce88f4cb5342567a6d35efa43ffd77752bf42b563</originalsourceid><addsrcrecordid>eNqNkl2L1DAUhoso7rr6D0QLguDFjM1n2xthWdQdWFjw6zak6UknY6YZk3Sx_97MTHeZgoLk4oRznnNy8vJm2UtULBEp0fuNG3wv7XLnelgWCBFWFY-yc1QTvOC4II9P7mfZsxA2RcFIxfnT7AwzitIdnWft9dh610Gfh8Fq00K-s3IMucx_wph7ZyE3fR7X-7A2jYnOj3kPg3fRyz5sTQjGJcAdmJ3pEpcqdxCMkjYfPETwz7MnWtoAL6Z4kX3_9PHb1fXi5vbz6uryZqFKjuMCMVYxRUgJnNUM8VLVsqCKKagqTVXDCMWMl5K3hIGWlGjdlmXJcKMpbhgnF9nr49yddUFMAgWBOOYVxrxEiVgdidbJjdh5s5V-FE4acUg43wnpo1EWRK1xTUlTEd0gWitUaS1rIFxDTRGoKs36ML02NFtoFew_bmdD55XerEXn7gTFtOCHdd9MA7z7NUCI_1h5ojqZtjK93iuvkvBKXFJUIVIXmCVq-RcqnRa2RiWLaJPys4Z3s4bERPgdOzmEIFZfv_w_e_tjzr49YdcgbVwHZ4eYbBLmID2CyrsQPOgH5VAh9g6_V0PsHS4mh6e2V6eqPzTdW5r8AbS39v8</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1626822671</pqid></control><display><type>article</type><title>Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Fernandes, Vítor S ; Ribeiro, Ana S F ; Martínez, Pilar ; López-Oliva, María Elvira ; Barahona, María Victoria ; Orensanz, Luis M ; Martínez-Sáenz, Ana ; Recio, Paz ; Benedito, Sara ; Bustamante, Salvador ; García-Sacristán, Albino ; Prieto, Dolores ; Hernández, Medardo</creator><creatorcontrib>Fernandes, Vítor S ; Ribeiro, Ana S F ; Martínez, Pilar ; López-Oliva, María Elvira ; Barahona, María Victoria ; Orensanz, Luis M ; Martínez-Sáenz, Ana ; Recio, Paz ; Benedito, Sara ; Bustamante, Salvador ; García-Sacristán, Albino ; Prieto, Dolores ; Hernández, Medardo</creatorcontrib><description>According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113580</identifier><identifier>PMID: 25415381</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology ; Activation ; Animals ; Arginine ; Biology ; Biology and Life Sciences ; Bladder ; Calcitonin ; Calcitonin gene-related peptide ; Capsaicin ; Capsaicin receptors ; Cystathionine beta-Synthase - metabolism ; Cystathionine gamma-Lyase - metabolism ; Desensitization ; Female ; Glibenclamide ; Hydrogen ; Hydrogen ion concentration ; Hydrogen sulfide ; Hydrogen Sulfide - metabolism ; Immunohistochemistry ; Intestine ; Ion channels ; Male ; Membranes ; Morpholines - pharmacology ; Muscle contraction ; Muscle, Smooth - enzymology ; Muscles ; Nervous system ; Neuropeptides ; Neuropeptides - metabolism ; Neurotransmission ; Nitric oxide ; Nitric-oxide synthase ; Organothiophosphorus Compounds - pharmacology ; Pituitary ; Pituitary adenylate cyclase-activating polypeptide ; Receptors ; Rodents ; Smooth muscle ; Sulfide ; Swine ; Synaptic Transmission - drug effects ; Thromboxane A2 ; Transient receptor potential proteins ; Ureter ; Ureter - cytology ; Ureter - enzymology ; Urogenital system ; Vasoactive agents ; Vasoactive intestinal peptide ; Vasoconstrictor Agents - pharmacology</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113580</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Fernandes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Fernandes et al 2014 Fernandes et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c762t-15585c337e6595167c9a04c5ce88f4cb5342567a6d35efa43ffd77752bf42b563</citedby><cites>FETCH-LOGICAL-c762t-15585c337e6595167c9a04c5ce88f4cb5342567a6d35efa43ffd77752bf42b563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240656/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240656/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25415381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fernandes, Vítor S</creatorcontrib><creatorcontrib>Ribeiro, Ana S F</creatorcontrib><creatorcontrib>Martínez, Pilar</creatorcontrib><creatorcontrib>López-Oliva, María Elvira</creatorcontrib><creatorcontrib>Barahona, María Victoria</creatorcontrib><creatorcontrib>Orensanz, Luis M</creatorcontrib><creatorcontrib>Martínez-Sáenz, Ana</creatorcontrib><creatorcontrib>Recio, Paz</creatorcontrib><creatorcontrib>Benedito, Sara</creatorcontrib><creatorcontrib>Bustamante, Salvador</creatorcontrib><creatorcontrib>García-Sacristán, Albino</creatorcontrib><creatorcontrib>Prieto, Dolores</creatorcontrib><creatorcontrib>Hernández, Medardo</creatorcontrib><title>Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.</description><subject>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology</subject><subject>Activation</subject><subject>Animals</subject><subject>Arginine</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Bladder</subject><subject>Calcitonin</subject><subject>Calcitonin gene-related peptide</subject><subject>Capsaicin</subject><subject>Capsaicin receptors</subject><subject>Cystathionine beta-Synthase - metabolism</subject><subject>Cystathionine gamma-Lyase - metabolism</subject><subject>Desensitization</subject><subject>Female</subject><subject>Glibenclamide</subject><subject>Hydrogen</subject><subject>Hydrogen ion concentration</subject><subject>Hydrogen sulfide</subject><subject>Hydrogen Sulfide - metabolism</subject><subject>Immunohistochemistry</subject><subject>Intestine</subject><subject>Ion channels</subject><subject>Male</subject><subject>Membranes</subject><subject>Morpholines - pharmacology</subject><subject>Muscle contraction</subject><subject>Muscle, Smooth - enzymology</subject><subject>Muscles</subject><subject>Nervous system</subject><subject>Neuropeptides</subject><subject>Neuropeptides - metabolism</subject><subject>Neurotransmission</subject><subject>Nitric oxide</subject><subject>Nitric-oxide synthase</subject><subject>Organothiophosphorus Compounds - pharmacology</subject><subject>Pituitary</subject><subject>Pituitary adenylate cyclase-activating polypeptide</subject><subject>Receptors</subject><subject>Rodents</subject><subject>Smooth muscle</subject><subject>Sulfide</subject><subject>Swine</subject><subject>Synaptic Transmission - drug effects</subject><subject>Thromboxane A2</subject><subject>Transient receptor potential proteins</subject><subject>Ureter</subject><subject>Ureter - cytology</subject><subject>Ureter - enzymology</subject><subject>Urogenital system</subject><subject>Vasoactive agents</subject><subject>Vasoactive intestinal peptide</subject><subject>Vasoconstrictor Agents - pharmacology</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguDFjM1n2xthWdQdWFjw6zak6UknY6YZk3Sx_97MTHeZgoLk4oRznnNy8vJm2UtULBEp0fuNG3wv7XLnelgWCBFWFY-yc1QTvOC4II9P7mfZsxA2RcFIxfnT7AwzitIdnWft9dh610Gfh8Fq00K-s3IMucx_wph7ZyE3fR7X-7A2jYnOj3kPg3fRyz5sTQjGJcAdmJ3pEpcqdxCMkjYfPETwz7MnWtoAL6Z4kX3_9PHb1fXi5vbz6uryZqFKjuMCMVYxRUgJnNUM8VLVsqCKKagqTVXDCMWMl5K3hIGWlGjdlmXJcKMpbhgnF9nr49yddUFMAgWBOOYVxrxEiVgdidbJjdh5s5V-FE4acUg43wnpo1EWRK1xTUlTEd0gWitUaS1rIFxDTRGoKs36ML02NFtoFew_bmdD55XerEXn7gTFtOCHdd9MA7z7NUCI_1h5ojqZtjK93iuvkvBKXFJUIVIXmCVq-RcqnRa2RiWLaJPys4Z3s4bERPgdOzmEIFZfv_w_e_tjzr49YdcgbVwHZ4eYbBLmID2CyrsQPOgH5VAh9g6_V0PsHS4mh6e2V6eqPzTdW5r8AbS39v8</recordid><startdate>20141121</startdate><enddate>20141121</enddate><creator>Fernandes, Vítor S</creator><creator>Ribeiro, Ana S F</creator><creator>Martínez, Pilar</creator><creator>López-Oliva, María Elvira</creator><creator>Barahona, María Victoria</creator><creator>Orensanz, Luis M</creator><creator>Martínez-Sáenz, Ana</creator><creator>Recio, Paz</creator><creator>Benedito, Sara</creator><creator>Bustamante, Salvador</creator><creator>García-Sacristán, Albino</creator><creator>Prieto, Dolores</creator><creator>Hernández, Medardo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141121</creationdate><title>Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter</title><author>Fernandes, Vítor S ; Ribeiro, Ana S F ; Martínez, Pilar ; López-Oliva, María Elvira ; Barahona, María Victoria ; Orensanz, Luis M ; Martínez-Sáenz, Ana ; Recio, Paz ; Benedito, Sara ; Bustamante, Salvador ; García-Sacristán, Albino ; Prieto, Dolores ; Hernández, Medardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c762t-15585c337e6595167c9a04c5ce88f4cb5342567a6d35efa43ffd77752bf42b563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology</topic><topic>Activation</topic><topic>Animals</topic><topic>Arginine</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Bladder</topic><topic>Calcitonin</topic><topic>Calcitonin gene-related peptide</topic><topic>Capsaicin</topic><topic>Capsaicin receptors</topic><topic>Cystathionine beta-Synthase - metabolism</topic><topic>Cystathionine gamma-Lyase - metabolism</topic><topic>Desensitization</topic><topic>Female</topic><topic>Glibenclamide</topic><topic>Hydrogen</topic><topic>Hydrogen ion concentration</topic><topic>Hydrogen sulfide</topic><topic>Hydrogen Sulfide - metabolism</topic><topic>Immunohistochemistry</topic><topic>Intestine</topic><topic>Ion channels</topic><topic>Male</topic><topic>Membranes</topic><topic>Morpholines - pharmacology</topic><topic>Muscle contraction</topic><topic>Muscle, Smooth - enzymology</topic><topic>Muscles</topic><topic>Nervous system</topic><topic>Neuropeptides</topic><topic>Neuropeptides - metabolism</topic><topic>Neurotransmission</topic><topic>Nitric oxide</topic><topic>Nitric-oxide synthase</topic><topic>Organothiophosphorus Compounds - pharmacology</topic><topic>Pituitary</topic><topic>Pituitary adenylate cyclase-activating polypeptide</topic><topic>Receptors</topic><topic>Rodents</topic><topic>Smooth muscle</topic><topic>Sulfide</topic><topic>Swine</topic><topic>Synaptic Transmission - drug effects</topic><topic>Thromboxane A2</topic><topic>Transient receptor potential proteins</topic><topic>Ureter</topic><topic>Ureter - cytology</topic><topic>Ureter - enzymology</topic><topic>Urogenital system</topic><topic>Vasoactive agents</topic><topic>Vasoactive intestinal peptide</topic><topic>Vasoconstrictor Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fernandes, Vítor S</creatorcontrib><creatorcontrib>Ribeiro, Ana S F</creatorcontrib><creatorcontrib>Martínez, Pilar</creatorcontrib><creatorcontrib>López-Oliva, María Elvira</creatorcontrib><creatorcontrib>Barahona, María Victoria</creatorcontrib><creatorcontrib>Orensanz, Luis M</creatorcontrib><creatorcontrib>Martínez-Sáenz, Ana</creatorcontrib><creatorcontrib>Recio, Paz</creatorcontrib><creatorcontrib>Benedito, Sara</creatorcontrib><creatorcontrib>Bustamante, Salvador</creatorcontrib><creatorcontrib>García-Sacristán, Albino</creatorcontrib><creatorcontrib>Prieto, Dolores</creatorcontrib><creatorcontrib>Hernández, Medardo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fernandes, Vítor S</au><au>Ribeiro, Ana S F</au><au>Martínez, Pilar</au><au>López-Oliva, María Elvira</au><au>Barahona, María Victoria</au><au>Orensanz, Luis M</au><au>Martínez-Sáenz, Ana</au><au>Recio, Paz</au><au>Benedito, Sara</au><au>Bustamante, Salvador</au><au>García-Sacristán, Albino</au><au>Prieto, Dolores</au><au>Hernández, Medardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-21</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113580</spage><pages>e113580-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>According to previous observations nitric oxide (NO), as well as an unknown nature mediator are involved in the inhibitory neurotransmission to the intravesical ureter. This study investigates the hydrogen sulfide (H2S) role in the neurogenic relaxation of the pig intravesical ureter. We have performed western blot and immunohistochemistry to study the expression of the H2S synthesis enzymes cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS), measurement of enzymatic production of H2S and myographic studies for isometric force recording. Immunohistochemical assays showed a high CSE expression in the intravesical ureter muscular layer, as well as a strong CSE-immunoreactivity within nerve fibres distributed along smooth muscle bundles. CBS expression, however, was not consistently observed. On ureteral strips precontracted with thromboxane A2 analogue U46619, electrical field stimulation (EFS) and the H2S donor P-(4-methoxyphenyl)-P-4-morpholinylphosphinodithioic acid (GYY4137) evoked frequency- and concentration-dependent relaxations. CSE inhibition with DL-propargylglycine (PPG) reduced EFS-elicited responses and a combined blockade of both CSE and NO synthase (NOS) with, respectively, PPG and NG-nitro-L-arginine (L-NOARG), greatly reduced such relaxations. Endogenous H2S production rate was reduced by PPG, rescued by addition of GYY4137 and was not changed by L-NOARG. EFS and GYY4137 relaxations were also reduced by capsaicin-sensitive primary afferents (CSPA) desensitization with capsaicin and blockade of ATP-dependent K+ (KATP) channels, transient receptor potential A1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), vasoactive intestinal peptide/pituitary adenylyl cyclase-activating polypeptide (VIP/PACAP) and calcitonin gene-related peptide (CGRP) receptors with glibenclamide, HC030031, AMG9810, PACAP6-38 and CGRP8-37, respectively. These results suggest that H2S, synthesized by CSE, is involved in the inhibitory neurotransmission to the pig intravesical ureter, through an NO-independent pathway, producing smooth muscle relaxation via KATP channel activation. H2S also promotes the release of inhibitory neuropeptides, as PACAP 38 and/or CGRP from CSPA through TRPA1, TRPV1 and related ion channel activation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25415381</pmid><doi>10.1371/journal.pone.0113580</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PloS one, 2014-11, Vol.9 (11), p.e113580
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1626822671
source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology
Activation
Animals
Arginine
Biology
Biology and Life Sciences
Bladder
Calcitonin
Calcitonin gene-related peptide
Capsaicin
Capsaicin receptors
Cystathionine beta-Synthase - metabolism
Cystathionine gamma-Lyase - metabolism
Desensitization
Female
Glibenclamide
Hydrogen
Hydrogen ion concentration
Hydrogen sulfide
Hydrogen Sulfide - metabolism
Immunohistochemistry
Intestine
Ion channels
Male
Membranes
Morpholines - pharmacology
Muscle contraction
Muscle, Smooth - enzymology
Muscles
Nervous system
Neuropeptides
Neuropeptides - metabolism
Neurotransmission
Nitric oxide
Nitric-oxide synthase
Organothiophosphorus Compounds - pharmacology
Pituitary
Pituitary adenylate cyclase-activating polypeptide
Receptors
Rodents
Smooth muscle
Sulfide
Swine
Synaptic Transmission - drug effects
Thromboxane A2
Transient receptor potential proteins
Ureter
Ureter - cytology
Ureter - enzymology
Urogenital system
Vasoactive agents
Vasoactive intestinal peptide
Vasoconstrictor Agents - pharmacology
title Hydrogen sulfide plays a key role in the inhibitory neurotransmission to the pig intravesical ureter
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T02%3A09%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hydrogen%20sulfide%20plays%20a%20key%20role%20in%20the%20inhibitory%20neurotransmission%20to%20the%20pig%20intravesical%20ureter&rft.jtitle=PloS%20one&rft.au=Fernandes,%20V%C3%ADtor%20S&rft.date=2014-11-21&rft.volume=9&rft.issue=11&rft.spage=e113580&rft.pages=e113580-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0113580&rft_dat=%3Cgale_plos_%3EA418139025%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1626822671&rft_id=info:pmid/25415381&rft_galeid=A418139025&rft_doaj_id=oai_doaj_org_article_9f2943b83fb149c18ffa9e36fe941ec8&rfr_iscdi=true