Inhibitory Effects of Gamma-Linolenic Acid on the Contractile Responses of Guinea Pig Ileal Longitudinal Smooth Muscle
Abstract
Gamma-linolenic acid (GLA), an n-6 polyunsaturated fatty acid, has been reported to influence gastrointestinal function after prolonged exposure. However, its direct effects on gastrointestinal smooth muscle contractility remain unclear. We examined the effects of GLA on receptor-mediated and depolarization-induced contractions in the guinea pig ileal longitudinal smooth muscle (ILSM) and explored the underlying intracellular signaling mechanisms. GLA (10–60 μM) concentration-dependently inhibited acetylcholine (ACh)- and histamine-induced contractions, causing rightward shifts of the concentration–response curves and reductions in the maximal responses, with a greater rightward shift observed for ACh. Inhibition by 10–30 μM GLA was largely reversible, whereas that by 60 μM GLA was only partially reversible. GLA (30–60 μM) also suppressed 80 mM potassium chloride (KCl)-induced contractions. ACh- and histamine-induced contractions were sensitive to the L-type Ca2+ channel (LCC) inhibitor verapamil. However, in A7r5 cells, GLA (60 μM) did not attenuate the high-KCl–evoked Ca2+ elevation, which was sensitive to verapamil. In A7r5 cells, GLA reduced the phosphorylation of both myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1) under basal and depolarizing conditions. GLA also inhibited [3H]N-methylscopolamine binding to muscarinic receptors in the mouse cerebral cortex. Collectively, these findings suggest that GLA suppresses ILSM contraction through intracellular mechanisms downstream of Ca2+ entry, which are associated with reduced phosphorylation of MLC and MYPT1, while additional muscarinic receptor inhibition may contribute to the greater suppression of ACh-induced contraction.
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BibTeX
@article{obara2026inhibitory,
title = {{Inhibitory Effects of Gamma-Linolenic Acid on the Contractile Responses of Guinea Pig Ileal Longitudinal Smooth Muscle}},
author = {Keisuke Obara and Nagisa Akemura and Mari Tanino and Qianghaodi Hong and Sakika Ichihara and Aya Shimada and Haruna Mori and Yukino Yamazaki and Ayano Yashiro and Kento Yoshioka and Noritaka Nakamichi and Yoshio Tanaka},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = oct,
doi = {10.1248/bpb.b26-00167},
url = {https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00167/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Inhibitory Effects of Gamma-Linolenic Acid on the Contractile Responses of Guinea Pig Ileal Longitudinal Smooth Muscle
AU - Keisuke Obara
AU - Nagisa Akemura
AU - Mari Tanino
AU - Qianghaodi Hong
AU - Sakika Ichihara
AU - Aya Shimada
AU - Haruna Mori
AU - Yukino Yamazaki
AU - Ayano Yashiro
AU - Kento Yoshioka
AU - Noritaka Nakamichi
AU - Yoshio Tanaka
PY - 2026
DA - 2026/10/28
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00167
UR - https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00167/_article
AB - Gamma-linolenic acid (GLA), an n-6 polyunsaturated fatty acid, has been reported to influence gastrointestinal function after prolonged exposure. However, its direct effects on gastrointestinal smooth muscle contractility remain unclear. We examined the effects of GLA on receptor-mediated and depolarization-induced contractions in the guinea pig ileal longitudinal smooth muscle (ILSM) and explored the underlying intracellular signaling mechanisms. GLA (10–60 μM) concentration-dependently inhibited acetylcholine (ACh)- and histamine-induced contractions, causing rightward shifts of the concentration–response curves and reductions in the maximal responses, with a greater rightward shift observed for ACh. Inhibition by 10–30 μM GLA was largely reversible, whereas that by 60 μM GLA was only partially reversible. GLA (30–60 μM) also suppressed 80 mM potassium chloride (KCl)-induced contractions. ACh- and histamine-induced contractions were sensitive to the L-type Ca2+ channel (LCC) inhibitor verapamil. However, in A7r5 cells, GLA (60 μM) did not attenuate the high-KCl–evoked Ca2+ elevation, which was sensitive to verapamil. In A7r5 cells, GLA reduced the phosphorylation of both myosin light chain (MLC) and myosin phosphatase target subunit 1 (MYPT1) under basal and depolarizing conditions. GLA also inhibited [3H]N-methylscopolamine binding to muscarinic receptors in the mouse cerebral cortex. Collectively, these findings suggest that GLA suppresses ILSM contraction through intracellular mechanisms downstream of Ca2+ entry, which are associated with reduced phosphorylation of MLC and MYPT1, while additional muscarinic receptor inhibition may contribute to the greater suppression of ACh-induced contraction.
SN - 1347-5215
SN - 0918-6158
ER -