Inhibitory Effects of Fatty Acids on Orai1-Mediated Contraction in Guinea Pig Gastric Fundus Smooth Muscle and Store-Operated Ca²⁺ Entry in 293T Cells
Abstract
Store-operated Ca2+ entry (SOCE), mediated by stromal interaction molecule (STIM) and Orai proteins, plays a key role in smooth muscle contraction. We previously demonstrated that docosahexaenoic acid (DHA) inhibits Orai1-dependent SOCE and suppresses contraction in guinea pig gastric fundus smooth muscle. However, whether this effect is specific to DHA or shared by other fatty acids remains unclear. In the present study, we examined the effects of thirteen fatty acids on cyclopiazonic acid (CPA)-induced contraction in gastric fundus smooth muscle and SOCE-associated Ca2+ responses in 293T cells. Among the fatty acids tested, γ-linolenic acid, pinolenic acid, eicosapentaenoic acid (EPA), and DHA significantly inhibited CPA-induced contraction. These fatty acids also suppressed SOCE-associated Ca2+ entry in wild-type 293T cells, with DHA showing the greatest effect. In STIM2-overexpressing 293T cells, pinolenic acid, EPA, and DHA inhibited SOCE-associated Ca2+ responses, whereas the inhibitory effect of γ-linolenic acid was lost. A structure–activity relationship was suggested, with inhibitory effects associated with the position of the first double bond relative to the carboxyl group (Δ4–Δ6). These findings suggest that fatty acids differentially inhibit SOCE, with pinolenic acid, EPA, and DHA showing consistent inhibitory effects across both 293T cell models, whereas γ-linolenic acid shows greater context dependence.
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BibTeX
@article{obara2026inhibitory,
title = {{Inhibitory Effects of Fatty Acids on Orai1-Mediated Contraction in Guinea Pig Gastric Fundus Smooth Muscle and Store-Operated Ca²⁺ Entry in 293T Cells}},
author = {Keisuke Obara and Kento Yoshioka and Natsuho Ishii and Naho Takazakura and Taichi Kusakabe and Keisuke Takahashi and Keisuke Kato and Noritaka Nakamichi and Yoshio Tanaka},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = oct,
doi = {10.1248/bpb.b26-00184},
url = {https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00184/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Inhibitory Effects of Fatty Acids on Orai1-Mediated Contraction in Guinea Pig Gastric Fundus Smooth Muscle and Store-Operated Ca²⁺ Entry in 293T Cells
AU - Keisuke Obara
AU - Kento Yoshioka
AU - Natsuho Ishii
AU - Naho Takazakura
AU - Taichi Kusakabe
AU - Keisuke Takahashi
AU - Keisuke Kato
AU - Noritaka Nakamichi
AU - Yoshio Tanaka
PY - 2026
DA - 2026/10/03
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00184
UR - https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00184/_article
AB - Store-operated Ca2+ entry (SOCE), mediated by stromal interaction molecule (STIM) and Orai proteins, plays a key role in smooth muscle contraction. We previously demonstrated that docosahexaenoic acid (DHA) inhibits Orai1-dependent SOCE and suppresses contraction in guinea pig gastric fundus smooth muscle. However, whether this effect is specific to DHA or shared by other fatty acids remains unclear. In the present study, we examined the effects of thirteen fatty acids on cyclopiazonic acid (CPA)-induced contraction in gastric fundus smooth muscle and SOCE-associated Ca2+ responses in 293T cells. Among the fatty acids tested, γ-linolenic acid, pinolenic acid, eicosapentaenoic acid (EPA), and DHA significantly inhibited CPA-induced contraction. These fatty acids also suppressed SOCE-associated Ca2+ entry in wild-type 293T cells, with DHA showing the greatest effect. In STIM2-overexpressing 293T cells, pinolenic acid, EPA, and DHA inhibited SOCE-associated Ca2+ responses, whereas the inhibitory effect of γ-linolenic acid was lost. A structure–activity relationship was suggested, with inhibitory effects associated with the position of the first double bond relative to the carboxyl group (Δ4–Δ6). These findings suggest that fatty acids differentially inhibit SOCE, with pinolenic acid, EPA, and DHA showing consistent inhibitory effects across both 293T cell models, whereas γ-linolenic acid shows greater context dependence.
SN - 1347-5215
SN - 0918-6158
ER -