Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle

• Published in: Scientific reports 2024-05, Vol.14 (1), p.11720-11720, Article 11720
• Main Authors: Xu, Keyue, Shimizu, Miyuki, Yamashita, Toma, Fujiwara, Mako, Oikawa, Shunya, Ou, Guanghan, Takazakura, Naho, Kusakabe, Taichi, Takahashi, Keisuke, Kato, Keisuke, Yoshioka, Kento, Obara, Keisuke, Tanaka, Yoshio
• Format: Article
• Language: English
• Subjects: 631/45/287/1183; 692/4020/2741/533; Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Animals; Bradykinin; Bradykinin - pharmacology; Calcium (intracellular); Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium channels; Calcium channels (voltage-gated); Calcium Channels - metabolism; Calcium influx; Carbachol; Carbachol - pharmacology; Cyclopiazonic acid; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Gastric Fundus - drug effects; Gastric Fundus - metabolism; Gastric Fundus - physiology; Guinea Pigs; HEK293 Cells; Humanities and Social Sciences; Humans; Imidazoles - pharmacology; Male; multidisciplinary; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Muscle, Smooth - physiology; Science; Science (multidisciplinary); Smooth muscle; Stomach; Verapamil; Verapamil - pharmacology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62578-y

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 Ca 2+ 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 Ca 2+ , more than 80% of BK-induced contractions remained even in the presence of verapamil, a voltage-dependent Ca 2+ channel inhibitor. BK-induced contractions in the presence of verapamil were not suppressed by LOE-908 (a receptor-operated Ca 2+ 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 Ca 2+ increase due to Ca 2+ addition in CPA-treated 293T cells. These findings indicate that Ca 2+ 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.