Abstract

We studied the inhibitory actions of docosahexaenoic acid (DHA) on the contractions induced by carbachol (CCh), angiotensin II (Ang II), and bradykinin (BK) in guinea pig (GP) gastric fundus smooth muscle (GFSM), particularly focusing on the possible inhibition of store-operated Ca2+ channels (SOCCs). DHA significantly suppressed the contractions induced by CCh, Ang II, and BK; the inhibition of BK-induced contractions was the strongest. Although all contractions were greatly dependent on external Ca2+, more than 80% of BK-induced contractions remained even in the presence of verapamil, a voltage-dependent Ca2+ channel inhibitor. BK-induced contractions in the presence of verapamil were not suppressed by LOE-908 (a receptor-operated Ca2+ channel (ROCC) inhibitor) but were suppressed by SKF-96365 (an SOCC and ROCC inhibitor). BK-induced contractions in the presence of verapamil plus LOE-908 were strongly inhibited by DHA. Furthermore, DHA inhibited GFSM contractions induced by cyclopiazonic acid (CPA) in the presence of verapamil plus LOE-908 and inhibited the intracellular Ca2+ increase due to Ca2+ addition in CPA-treated 293T cells. These findings indicate that Ca2+ influx through SOCCs plays a crucial role in BK-induced contraction in GP GFSM and that this inhibition by DHA is a new mechanism by which this fatty acid inhibits GFSM contractions.

Details

Title
Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle
Author
Xu, Keyue 1 ; Shimizu, Miyuki 1 ; Yamashita, Toma 1 ; Fujiwara, Mako 1 ; Oikawa, Shunya 1 ; Ou, Guanghan 1 ; Takazakura, Naho 1 ; Kusakabe, Taichi 2 ; Takahashi, Keisuke 2 ; Kato, Keisuke 2 ; Yoshioka, Kento 1 ; Obara, Keisuke 1 ; Tanaka, Yoshio 1 

 Toho University, Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Funabashi-City, Japan (GRID:grid.265050.4) (ISNI:0000 0000 9290 9879) 
 Toho University, Department of Organic Chemistry, Faculty of Pharmaceutical Sciences, Funabashi-City, Japan (GRID:grid.265050.4) (ISNI:0000 0000 9290 9879) 
Pages
11720
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3058372948
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.