Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus
Aim Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store‐operated channels. There are reports that these proteins mediate agonist‐induced Ca2+ influx in cultured m...
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| Veröffentlicht in: | The journal of obstetrics and gynaecology research 2021-12, Vol.47 (12), p.4306-4318 |
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| container_issue | 12 |
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| container_title | The journal of obstetrics and gynaecology research |
| container_volume | 47 |
| creator | de Sousa, Ícaro Araújo de Meneses, Gabriel Medina Sobreira Cardoso, José Victor Miranda Lopes, Pablo Queiroz de Sousa, Joubert Aires Cavalcanti, Suzana Maria Pereira Galvão da Silva Cavalcanti, Paulo Marques Filho, Francisco Chagas |
| description | Aim
Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store‐operated channels. There are reports that these proteins mediate agonist‐induced Ca2+ influx in cultured myometrial cells. In this study, we aimed to determine the effects of Pyr6, an Orai channel blocker, on different agonist‐induced contractions in isolated segments of rat uterus.
Main findings
In Ca2+‐free Tyrode's solution, Pyr6 (3 μM) promoted a reduction in both the magnitude and frequency of Ca2+ (1 mM)‐induced uterine contractions after the addition of carbachol (CCh, 100 μM), but not after the addition of oxytocin (OT, 150 nM). In Ca2+ (0.18 mM)‐Tyrode's solution, Pyr6 completely relaxed uterine contractions induced by both CCh and cloprostenol (300 nM), but not those induced by either KCI (40–80 mM) or OT. The addition of Pyr6 abolished the oscillatory uterine contractions induced by Ca2+ after the addition of cyclopiazonic acid (CPA, 10 μM). When pre‐incubated (5 min), Pyr6 reduced the magnitude of both CCh‐induced phasic and tonic contractions. The addition of Pyr2 (3 μM), an Orai and TRPC channel blocker, abolished uterine contractions induced by CCh or OT.
Conclusion
Considering Pyr6 as an Orai channel blocker and its inhibitory effect on uterine contractions induced by CCh, CPA, and cloprostenol, we suggest that Orai channels are required for the maintenance of contractions induced by these agonists in rat uterus. |
| doi_str_mv | 10.1111/jog.15034 |
| format | Article |
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Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store‐operated channels. There are reports that these proteins mediate agonist‐induced Ca2+ influx in cultured myometrial cells. In this study, we aimed to determine the effects of Pyr6, an Orai channel blocker, on different agonist‐induced contractions in isolated segments of rat uterus.
Main findings
In Ca2+‐free Tyrode's solution, Pyr6 (3 μM) promoted a reduction in both the magnitude and frequency of Ca2+ (1 mM)‐induced uterine contractions after the addition of carbachol (CCh, 100 μM), but not after the addition of oxytocin (OT, 150 nM). In Ca2+ (0.18 mM)‐Tyrode's solution, Pyr6 completely relaxed uterine contractions induced by both CCh and cloprostenol (300 nM), but not those induced by either KCI (40–80 mM) or OT. The addition of Pyr6 abolished the oscillatory uterine contractions induced by Ca2+ after the addition of cyclopiazonic acid (CPA, 10 μM). When pre‐incubated (5 min), Pyr6 reduced the magnitude of both CCh‐induced phasic and tonic contractions. The addition of Pyr2 (3 μM), an Orai and TRPC channel blocker, abolished uterine contractions induced by CCh or OT.
Conclusion
Considering Pyr6 as an Orai channel blocker and its inhibitory effect on uterine contractions induced by CCh, CPA, and cloprostenol, we suggest that Orai channels are required for the maintenance of contractions induced by these agonists in rat uterus.</description><identifier>ISSN: 1341-8076</identifier><identifier>EISSN: 1447-0756</identifier><identifier>DOI: 10.1111/jog.15034</identifier><identifier>PMID: 34571573</identifier><language>eng</language><publisher>Kyoto, Japan: John Wiley & Sons Australia, Ltd</publisher><subject>Agonists ; Animals ; Calcium channels ; Calcium influx ; Carbachol ; Cyclopiazonic acid ; Female ; Myometrium ; Orai channels ; Oxytocin ; Pregnancy ; Pyr6 ; rat uterus ; Rats ; Transient receptor potential proteins ; TRPC channels ; Uterine Contraction ; uterine contractions ; Uterus</subject><ispartof>The journal of obstetrics and gynaecology research, 2021-12, Vol.47 (12), p.4306-4318</ispartof><rights>2021 Japan Society of Obstetrics and Gynecology.</rights><rights>2021 Japan Society of Obstetrics and Gynecology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3374-2bfa020336fca19cdcac64e4a4a0fb23d3b07261d4915fec2b8c54e562a630b33</cites><orcidid>0000-0002-6674-3523</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjog.15034$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjog.15034$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34571573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>de Sousa, Ícaro Araújo</creatorcontrib><creatorcontrib>de Meneses, Gabriel Medina Sobreira</creatorcontrib><creatorcontrib>Cardoso, José Victor Miranda</creatorcontrib><creatorcontrib>Lopes, Pablo Queiroz</creatorcontrib><creatorcontrib>de Sousa, Joubert Aires</creatorcontrib><creatorcontrib>Cavalcanti, Suzana Maria Pereira Galvão</creatorcontrib><creatorcontrib>da Silva Cavalcanti, Paulo Marques</creatorcontrib><creatorcontrib>Filho, Francisco Chagas</creatorcontrib><title>Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus</title><title>The journal of obstetrics and gynaecology research</title><addtitle>J Obstet Gynaecol Res</addtitle><description>Aim
Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store‐operated channels. There are reports that these proteins mediate agonist‐induced Ca2+ influx in cultured myometrial cells. In this study, we aimed to determine the effects of Pyr6, an Orai channel blocker, on different agonist‐induced contractions in isolated segments of rat uterus.
Main findings
In Ca2+‐free Tyrode's solution, Pyr6 (3 μM) promoted a reduction in both the magnitude and frequency of Ca2+ (1 mM)‐induced uterine contractions after the addition of carbachol (CCh, 100 μM), but not after the addition of oxytocin (OT, 150 nM). In Ca2+ (0.18 mM)‐Tyrode's solution, Pyr6 completely relaxed uterine contractions induced by both CCh and cloprostenol (300 nM), but not those induced by either KCI (40–80 mM) or OT. The addition of Pyr6 abolished the oscillatory uterine contractions induced by Ca2+ after the addition of cyclopiazonic acid (CPA, 10 μM). When pre‐incubated (5 min), Pyr6 reduced the magnitude of both CCh‐induced phasic and tonic contractions. The addition of Pyr2 (3 μM), an Orai and TRPC channel blocker, abolished uterine contractions induced by CCh or OT.
Conclusion
Considering Pyr6 as an Orai channel blocker and its inhibitory effect on uterine contractions induced by CCh, CPA, and cloprostenol, we suggest that Orai channels are required for the maintenance of contractions induced by these agonists in rat uterus.</description><subject>Agonists</subject><subject>Animals</subject><subject>Calcium channels</subject><subject>Calcium influx</subject><subject>Carbachol</subject><subject>Cyclopiazonic acid</subject><subject>Female</subject><subject>Myometrium</subject><subject>Orai channels</subject><subject>Oxytocin</subject><subject>Pregnancy</subject><subject>Pyr6</subject><subject>rat uterus</subject><subject>Rats</subject><subject>Transient receptor potential proteins</subject><subject>TRPC channels</subject><subject>Uterine Contraction</subject><subject>uterine contractions</subject><subject>Uterus</subject><issn>1341-8076</issn><issn>1447-0756</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kLtOwzAUhi0E4lIYeAFkiQWGUN_djKiCUoRUBpgjx3GKS2qDnQhl4xF4Rp4EQ4ABibOcM3zn068fgEOMznCa8covzzBHlG2AXcyYzJDkYjPdlOFsgqTYAXsxrhDCMseTbbBDGZeYS7oL9Nw92NK2PvTQ1LXRLfQ1vO2DgCfKwUVQFuoH5ZxpYNl4_WjCKfQOqqV3Nrbvr2_WVZ02FdTetUHp1noXoXUwqBZ2rQld3AdbtWqiOfjeI3B_eXE3vcpuFrP59Pwm05RKlpGyVoggSkWtFc51pZUWzDDFFKpLQitaIkkErliOeUpKyonmzHBBlKCopHQETgbvU_DPnYltsbZRm6ZRzvguFoRLyVhOOU_o8R905bvgUrqCCMRyQolEiTodKB18jMHUxVOwaxX6AqPis_n0tSy-mk_s0bexK9em-iV_qk7AeABebGP6_03F9WI2KD8AVS-NWw</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>de Sousa, Ícaro Araújo</creator><creator>de Meneses, Gabriel Medina Sobreira</creator><creator>Cardoso, José Victor Miranda</creator><creator>Lopes, Pablo Queiroz</creator><creator>de Sousa, Joubert Aires</creator><creator>Cavalcanti, Suzana Maria Pereira Galvão</creator><creator>da Silva Cavalcanti, Paulo Marques</creator><creator>Filho, Francisco Chagas</creator><general>John Wiley & Sons Australia, Ltd</general><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>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6674-3523</orcidid></search><sort><creationdate>202112</creationdate><title>Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus</title><author>de Sousa, Ícaro Araújo ; de Meneses, Gabriel Medina Sobreira ; Cardoso, José Victor Miranda ; Lopes, Pablo Queiroz ; de Sousa, Joubert Aires ; Cavalcanti, Suzana Maria Pereira Galvão ; da Silva Cavalcanti, Paulo Marques ; Filho, Francisco Chagas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3374-2bfa020336fca19cdcac64e4a4a0fb23d3b07261d4915fec2b8c54e562a630b33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agonists</topic><topic>Animals</topic><topic>Calcium channels</topic><topic>Calcium influx</topic><topic>Carbachol</topic><topic>Cyclopiazonic acid</topic><topic>Female</topic><topic>Myometrium</topic><topic>Orai channels</topic><topic>Oxytocin</topic><topic>Pregnancy</topic><topic>Pyr6</topic><topic>rat uterus</topic><topic>Rats</topic><topic>Transient receptor potential proteins</topic><topic>TRPC channels</topic><topic>Uterine Contraction</topic><topic>uterine contractions</topic><topic>Uterus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>de Sousa, Ícaro Araújo</creatorcontrib><creatorcontrib>de Meneses, Gabriel Medina Sobreira</creatorcontrib><creatorcontrib>Cardoso, José Victor Miranda</creatorcontrib><creatorcontrib>Lopes, Pablo Queiroz</creatorcontrib><creatorcontrib>de Sousa, Joubert Aires</creatorcontrib><creatorcontrib>Cavalcanti, Suzana Maria Pereira Galvão</creatorcontrib><creatorcontrib>da Silva Cavalcanti, Paulo Marques</creatorcontrib><creatorcontrib>Filho, Francisco Chagas</creatorcontrib><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>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of obstetrics and gynaecology research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>de Sousa, Ícaro Araújo</au><au>de Meneses, Gabriel Medina Sobreira</au><au>Cardoso, José Victor Miranda</au><au>Lopes, Pablo Queiroz</au><au>de Sousa, Joubert Aires</au><au>Cavalcanti, Suzana Maria Pereira Galvão</au><au>da Silva Cavalcanti, Paulo Marques</au><au>Filho, Francisco Chagas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus</atitle><jtitle>The journal of obstetrics and gynaecology research</jtitle><addtitle>J Obstet Gynaecol Res</addtitle><date>2021-12</date><risdate>2021</risdate><volume>47</volume><issue>12</issue><spage>4306</spage><epage>4318</epage><pages>4306-4318</pages><issn>1341-8076</issn><eissn>1447-0756</eissn><abstract>Aim
Both human and rat myometrium express stromal interaction molecule (STIM) and Orai/transient receptor potential canonical (TRPC) proteins, which are components of plasma membrane Ca2+ store‐operated channels. There are reports that these proteins mediate agonist‐induced Ca2+ influx in cultured myometrial cells. In this study, we aimed to determine the effects of Pyr6, an Orai channel blocker, on different agonist‐induced contractions in isolated segments of rat uterus.
Main findings
In Ca2+‐free Tyrode's solution, Pyr6 (3 μM) promoted a reduction in both the magnitude and frequency of Ca2+ (1 mM)‐induced uterine contractions after the addition of carbachol (CCh, 100 μM), but not after the addition of oxytocin (OT, 150 nM). In Ca2+ (0.18 mM)‐Tyrode's solution, Pyr6 completely relaxed uterine contractions induced by both CCh and cloprostenol (300 nM), but not those induced by either KCI (40–80 mM) or OT. The addition of Pyr6 abolished the oscillatory uterine contractions induced by Ca2+ after the addition of cyclopiazonic acid (CPA, 10 μM). When pre‐incubated (5 min), Pyr6 reduced the magnitude of both CCh‐induced phasic and tonic contractions. The addition of Pyr2 (3 μM), an Orai and TRPC channel blocker, abolished uterine contractions induced by CCh or OT.
Conclusion
Considering Pyr6 as an Orai channel blocker and its inhibitory effect on uterine contractions induced by CCh, CPA, and cloprostenol, we suggest that Orai channels are required for the maintenance of contractions induced by these agonists in rat uterus.</abstract><cop>Kyoto, Japan</cop><pub>John Wiley & Sons Australia, Ltd</pub><pmid>34571573</pmid><doi>10.1111/jog.15034</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6674-3523</orcidid></addata></record> |
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| ispartof | The journal of obstetrics and gynaecology research, 2021-12, Vol.47 (12), p.4306-4318 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Agonists Animals Calcium channels Calcium influx Carbachol Cyclopiazonic acid Female Myometrium Orai channels Oxytocin Pregnancy Pyr6 rat uterus Rats Transient receptor potential proteins TRPC channels Uterine Contraction uterine contractions Uterus |
| title | Inhibitory effect of Pyr6 (an Orai channel blocker) on agonist‐induced contractions in rat uterus |
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