Mechanisms involved in the muscle relaxing effects of STW 5 in guinea pig stomach.

Autor: Allam S; Chair of Human Biology, Technical University of Munich, Freising, Germany.; Pharmacology and Toxicology Department, Faculty of Pharmacy, Menoufia University, Shebeen El-Kom, Egypt., Krüger D; Chair of Human Biology, Technical University of Munich, Freising, Germany., Michel K; Chair of Human Biology, Technical University of Munich, Freising, Germany., Schnabl K; Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany., Klingenspor M; Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Technical University of Munich, Freising, Germany., Schemann M; Chair of Human Biology, Technical University of Munich, Freising, Germany., Annaházi A; Chair of Human Biology, Technical University of Munich, Freising, Germany.; Chair of Zoology, Technical University of Munich, Freising, Germany.
Jazyk: angličtina
Zdroj: Neurogastroenterology and motility [Neurogastroenterol Motil] 2024 Oct; Vol. 36 (10), pp. e14761. Date of Electronic Publication: 2024 Feb 11.
DOI: 10.1111/nmo.14761
Abstrakt: Introduction: 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.
Methods: STW 5-induced 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.
Key Results: Blockade of Ca 2+ -activated K + and Cl - channels, voltage-gated L- or T-type Ca2+ channels, TRPA1-, TRPV1-, adenosine or 5-HT 4 receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5-evoked relaxation. Likewise, protein-kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol-12-myristat-13-acetat, an activator of protein-kinase C, by 2- aminoethyldiphenylborinate, an inhibitor of the IP3 receptor-mediated Ca 2+ release from the sarcoplasmic reticulum or by SKF-96365, a nonselective store-operated 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-coupled SOCE, almost abolished STW 5-evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus.
Conclusions & Inferences: STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3- and PKC-dependent 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.
(© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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