Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) inhibit the contractile response of smooth muscle in the lower gastrointestinal tract

DHA and EPA inhibit the contractile response dependent on voltage-gated Ca²⁺channels

A research group led by Dr. Keisuke Obara, Dr. Kento Yoshioka and Professor Yoshio Tanaka of the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, found that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in fish oil and have attracted increasing attention as health food ingredients, inhibit a wide variety of the contractile responses of the lower gastrointestinal smooth muscle, and that the inhibitory mechanism significantly involves the inhibition by DHA and EPA of the activation of voltage-gated Ca²⁺ channels. These research findings were recommended to be published as a Highlighted paper selected by the Editor-in-Chief and Featured Article in Biological and Pharmaceutical Bulletin and published on August 1, 2021.
The results were published on August 1, 2021. The findings were also selected as a cover illustration of the issue (Volume 44, Issue 8).

A research group led by Dr. Keisuke Obara, Dr. Kento Yoshioka and Professor Yoshio Tanaka of the Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, found that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are abundant in fish oil and have attracted increasing attention as health food ingredients, inhibit a wide variety of the contractile responses of the lower gastrointestinal smooth muscle, and that the inhibitory mechanism significantly involves the inhibition by DHA and EPA of the activation of voltage-gated Ca²⁺ channels. These research findings were recommended to be published as a Highlighted paper selected by the Editor-in-Chief and Featured Article in Biological and Pharmaceutical Bulletin and published on August 1, 2021. The results were published on August 1, 2021. The findings were also selected as a cover illustration of the issue (Volume 44, Issue 8).

Key points

Although DHA and EPA improve inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, owing to their anti-inflammatory effects, the effects of DHA and EPA on the motility of the lower gastrointestinal tract remain largely unknown.
In this study, we found that DHA and EPA inhibited a wide variety of the contractile responses of guinea pig longitudinal ileum and longitudinal colon muscles, and that this inhibition was related to their ability to inhibit responses depending on the activation of voltage-dependent Ca²⁺ channels.
These results suggest that DHA and EPA may improve the contractile dysfunction of the lower gastrointestinal tract associated with inflammatory diseases, by suppressing the contractile response of the ileum and colon, which is dependent on voltage-gated Ca²⁺ channels.

Summary
These n-3 polyunsaturated fatty acids have been reported to improve inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, owing to their anti-inflammatory effects. However, the effects of n-3 polyunsaturated fatty acids on the motility of the lower gastrointestinal tract, including the ileum and colon, the preferred site of these diseases, have not been extensively studied.
To clarify the effects of DHA and EPA on the motility of the lower gastrointestinal tract, the research group evaluated the effects of these fatty acids on the contractile response of the longitudinal muscles of the ileum and colon from guinea pigs.
The results showed that DHA and EPA non-specifically inhibited the contractile response of the longitudinal muscles of the ileum and colon induced by various bioactive substances, and that this inhibition was related to the ability of DHA and EPA to inhibit the responses largely related to the activation of the voltage-gated Ca²⁺ channels.
These findings suggest that DHA and EPA may ameliorate the contractile dysfunction of the lower gastrointestinal tract associated with inflammatory diseases, by inhibiting the contractile response of the ileum and colon, which is dependent on voltage-gated Ca²⁺ channels.

Authors: Keisuke Obara (Lecturer, Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University)
Kento Yoshioka (Assistant Professor, Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University)
Yoshio Tanaka (Professor, Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University)