Docosahexaenoic Acid and Eicosapentaenoic Acid Inhibit the Contractile Responses of the Guinea Pig Lower Gastrointestinal Tract

Abstract

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are n-3 polyunsaturated fatty acids (PUFAs), and are abundant in fish oil. These n-3 PUFAs have been reported to improve the lower gastrointestinal (LGI) disorders such as ulcerative colitis and Crohn's disease through their anti-inflammatory effects. However, there are few studies on the effect of n-3 PUFAs on motility of the LGI tract, such as the ileum and colon, the parts frequently affected by these inflammatory disorders. To elucidate the effects of DHA and EPA on the LGI tract motility, we performed comparative evaluation of their effects and linoleic acid (LA), an n-6 PUFA, on contractions in the ileal and colonic longitudinal smooth muscles (LSMs) isolated from guinea pigs. In the ileal and colonic LSMs, DHA and EPA (3 10 5 M each) significantly inhibited contractions induced by acetylcholine (ACh), histamine, and prostaglandin (PG) F 2α (vs. control), and these effects are stronger than that of LA (3 10 5 M). In the colonic LSMs, DHA and EPA also significantly inhibited contractions induced by PGD 2 (vs. control). In addition, DHA and EPA significantly inhibited CaCl 2 -induced ileal and colonic LSM contractions in Ca 2 -free 80 mM-KCl solution (vs. control). Any ileal and colonic LSM contractions induced by ACh, histamine, PGF 2α , and CaCl 2 were completely suppressed by verapamil (10 5 M), a voltage-gated/dependent Ca 2 channel (VGCC/VDCC) inhibitor. These findings suggest that DHA and EPA could improve the abnormal contractile functions of the LGI tract associated with inflammatory diseases, partly through inhibition of VGCC/VDCC-dependent ileal and colonic LSM contractions.

Docosahexaenoic acid and eicosapentaenoic acid strongly inhibit prostanoid TP receptor‐dependent contractions of guinea pig gastric fundus smooth muscle

“…Regarding the mechanisms of the immediate effects of DHA and EPA on the prostanoid‐induced contractile responses of GFSM, prostanoids have been reported previously to bind multiple prostanoid receptors, 25 and multiple prostanoid receptors were shown to mediate the stomach contractions induced by PGD 2 , PGE 2 , PGF 2α , and PGI 2 in knockout mice 12 . In addition, we have reported that DHA and EPA could affect verapamil‐sensitive Ca 2+ signaling pathways in the guinea pig's lower gastrointestinal tract, suggesting the involvement of L‐type Ca 2+ channels 26 . However, to the best of our knowledge, the prostanoid receptor subtypes and putative Ca 2+ signaling pathways in GFSM contractions have not been examined in guinea pigs to date.…”

“… 12 In addition, we have reported that DHA and EPA could affect verapamil ‐sensitive Ca 2+ signaling pathways in the guinea pig's lower gastrointestinal tract, suggesting the involvement of L‐type Ca 2+ channels. 26 However, to the best of our knowledge, the prostanoid receptor subtypes and putative Ca 2+ signaling pathways in GFSM contractions have not been examined in guinea pigs to date.…”

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

“…We have proposed TP receptor antagonism and functional inhibition of VDCCs as the mechanisms by which DHA produces immediate inhibitory activity against SM contractions induced by a TP receptor agonist/prostanoids and non-prostanoid agonists 8 – 11 , 17 , 18 . In addition, we now show that inhibition of SOCC-mediated Ca 2+ influx is a new mechanism responsible for the DHA-induced inhibition of SM contractions (Supplementary Fig.…”

“…Functional inhibition of voltage-dependent Ca 2+ channels (VDCCs) was also assumed to be partly responsible for the DHA-induced suppression of GFSM contractions by U46619 and prostanoids 17 . Furthermore, the functional inhibition of VDCCs was shown to be involved in the DHA inhibitory actions on GP ileal/colonic longitudinal SM contractions induced by some prostanoids 18 .…”

“…Regarding contractions induced by non-prostanoid biological substances such as acetylcholine and histamine, we previously showed that DHA partly inhibited their contractile effects on GP ileal/colonic longitudinal SMs by functionally inhibiting VDCCs 18 . We assumed that DHA would exhibit the same inhibitory actions against non-prostanoid substance-induced contractions even in GFSM.…”