{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:03:03Z","timestamp":1768906983688,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T00:00:00Z","timestamp":1707609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>STW 5\u2010induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Blockade of Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> and Cl<jats:sup>\u2212<\/jats:sup> channels, voltage\u2010gated L\u2010 or T\u2010type Ca2+ channels, TRPA1\u2010, TRPV1\u2010, adenosine or 5\u2010HT<jats:sub>4<\/jats:sub> receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5\u2010evoked relaxation. Likewise, protein\u2010kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol\u201012\u2010myristat\u201013\u2010acetat, an activator of protein\u2010kinase C, by 2\u2010 aminoethyldiphenylborinate, an inhibitor of the IP3 receptor\u2010mediated Ca<jats:sup>2+<\/jats:sup> release from the sarcoplasmic reticulum or by SKF\u201096365, a nonselective store\u2010operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3\/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI\u2010coupled SOCE, almost abolished STW 5\u2010evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus\/fundus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3\u2010 and PKC\u2010dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14761","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T04:25:10Z","timestamp":1707711910000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanisms involved in the muscle relaxing effects of STW 5 in guinea pig stomach"],"prefix":"10.1111","volume":"36","author":[{"given":"Shady","family":"Allam","sequence":"first","affiliation":[{"name":"Chair of Human Biology Technical University of Munich  Freising Germany"},{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Menoufia University  Shebeen El\u2010Kom Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Chair of Human Biology Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Michel","sequence":"additional","affiliation":[{"name":"Chair of Human Biology Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Schnabl","sequence":"additional","affiliation":[{"name":"Chair for Molecular Nutritional Medicine, TUM School of Life Sciences Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Klingenspor","sequence":"additional","affiliation":[{"name":"Chair for Molecular Nutritional Medicine, TUM School of Life Sciences Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Schemann","sequence":"additional","affiliation":[{"name":"Chair of Human Biology Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-8331","authenticated-orcid":false,"given":"Anita","family":"Annah\u00e1zi","sequence":"additional","affiliation":[{"name":"Chair of Human Biology Technical University of Munich  Freising Germany"},{"name":"Chair of Zoology Technical University of Munich  Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,11]]},"reference":[{"key":"e_1_2_13_1_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000485410"},{"key":"e_1_2_13_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2004.00548.x"},{"key":"e_1_2_13_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2006.03.020"},{"key":"e_1_2_13_1_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01142.x"},{"key":"e_1_2_13_1_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.085365"},{"key":"e_1_2_13_1_7_1","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.41.207"},{"key":"e_1_2_13_1_8_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i9.2054"},{"issue":"3","key":"e_1_2_13_1_9_1","first-page":"227","article-title":"Phasic and tonic types of smooth muscle activity in lower oesophageal sphincter and stomach of the dog","volume":"26","author":"Golenhofen K","year":"1979","journal-title":"Acta Hepatogastroenterol (Stuttg)"},{"key":"e_1_2_13_1_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920111793937862"},{"key":"e_1_2_13_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118112"},{"key":"e_1_2_13_1_12_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2018-0723"},{"key":"e_1_2_13_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00438-5"},{"key":"e_1_2_13_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2018.07.005"},{"issue":"5","key":"e_1_2_13_1_15_1","first-page":"235","article-title":"Indomethacin, but not helicobacter pylori, inhibits adaptive relaxation in isolated Guinea\u2010pig stomach","volume":"30","author":"Higuchi K","year":"2004","journal-title":"Drugs Exp. 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