Inhibitory Effects of the Constituents of Prunus mume on Bradykinin and Prostaglandin E2 Production in Abdominal Cavities of Mice

Prostaglandin E2 receptor EP4 is involved in inflammation and related tumorigenesis in the colorectum. This study aimed to investigate the chemopreventive ability of RQ-15986, a selective EP4 antagonist, in colitis-related colorectal tumorigenesis. Male Kyoto APC delta rats, which have APC mutations, were treated with azoxymethane and dextran sulfate sodium and subsequently administered RQ-15986 for eight weeks. At the end of the experiment, the development of colorectal tumor was significantly inhibited in the RQ-15986-treated group. The cell proliferation of the crypts and tumors in the colorectum was decreased following RQ-15986 treatment. RQ-15986 also suppressed the expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, interleukin-18, and monocyte chemotactic protein-1, in the colon mucosa. In addition, the expression levels of indoleamine 2,3-dioxygenase, which is involved in immune tolerance, were decreased in the colorectal epithelium and tumors of the RQ-15986-treated group. These findings indicate that RQ-15986 inhibits colitis-associated colorectal tumorigenesis by attenuating inflammation, suppressing cell proliferation, and modulating the expression of indoleamine 2,3-dioxygenase. Targeting prostaglandin E2/EP4 signaling might be a useful strategy for chemoprevention of inflammation-related colorectal cancer.

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Differential effects of prostaglandin E2 on contractions of airway smooth muscle

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.3.1397 ◽

1989 ◽

Vol 66 (3) ◽

pp. 1397-1407 ◽

Cited By ~ 3

Author(s):

J. M. Madison ◽

C. A. Jones ◽

R. M. Sankary ◽

J. K. Brown

Keyword(s):

Smooth Muscle ◽

Adenylate Cyclase ◽

Prostaglandin E2 ◽

Cyclase Activity ◽

Adenylate Cyclase Activity ◽

Tracheal Smooth Muscle ◽

Inhibitory Effects ◽

Camp Content

In an in vitro muscle bath, the active tension generated by strips of canine tracheal smooth muscle responding to cumulative additions of either histamine (10(-8) to 10(-3) M) or acetylcholine (10(-9) to 10(-3) M) was measured in the absence and presence of prostaglandin E2 (PGE2) (10(-6) to 10(-5) M). When contractile responses of equal magnitude were compared, the contractions elicited by acetylcholine were resistant to the inhibitory effects of PGE2, relative to comparable contractions elicited by histamine. To assess the role of adenylate cyclase in determining the different responses to histamine and acetylcholine in the presence of PGE2, we assayed adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and found that acetylcholine, but not histamine, decreased PGE2-stimulated adenylate cyclase activity by 48 +/- 2% (mean +/- SE; n = 5). However, in other experiments, we found that even large pharmacological increases in tissue adenosine 3′,5′-cyclic monophosphate (cAMP) content only partially inhibited muscarinic tone. Also, exogenously applied analogues of cyclic AMP inhibited contractions induced by histamine more effectively than comparable contractions induced by acetylcholine. We concluded that acetylcholine decreased adenylate cyclase activity in membranes prepared from canine tracheal smooth muscle and that this effect may have contributed to, but did not completely account for, the relative resistance of muscarinic contractions to the inhibitory effects of PGE2.

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Inhibitory Effects of Pectinase‐Treated Prunus Mume Fruit Concentrate on Colorectal Cancer Proliferation and Angiogenesis of Endothelial Cells

Journal of Food Science ◽

10.1111/1750-3841.14824 ◽

2019 ◽

Vol 84 (11) ◽

pp. 3284-3295 ◽

Cited By ~ 3

Author(s):

Hyun‐Dong Cho ◽

Jeong‐Ho Kim ◽

Yeong‐Seon Won ◽

Kwang‐Deok Moon ◽

Kwon‐Il Seo

Keyword(s):

Colorectal Cancer ◽

Endothelial Cells ◽

Prunus Mume ◽

Inhibitory Effects ◽

Cancer Proliferation

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Effect of Na-K adenosinetriphosphatase activity on relaxation of canine tracheal smooth muscle

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.2.635 ◽

1988 ◽

Vol 64 (2) ◽

pp. 635-641 ◽

Cited By ~ 33

Author(s):

S. J. Gunst ◽

J. Q. Stropp

Keyword(s):

Smooth Muscle ◽

Adenylate Cyclase ◽

Atpase Activity ◽

Prostaglandin E2 ◽

Sodium Nitroprusside ◽

Tracheal Smooth Muscle ◽

Free Medium ◽

Inhibitory Effects ◽

Ca2 Channels ◽

Stimulation Of

The effect of Na-K adenosinetriphosphatase (ATPase) on relaxation induced by isoproterenol, prostaglandin E2, sodium nitroprusside, and forskolin, a specific stimulant of adenylate cyclase, was investigated in canine tracheal smooth muscle strips. Relaxation in response to isoproterenol, prostaglandin E2, and forskolin was significantly decreased after inhibition of the Na-K ATPase by ouabain or a potassium-free medium, but relaxation to sodium nitroprusside was not affected. Relaxation to isoproterenol was greater in muscles contracted by 5-hydroxytryptamine than in those contracted by acetylcholine. The stimulation of Na-K ATPase activity with potassium also caused differences in relaxation between tissues contracted with 5-hydroxytryptamine or acetylcholine. Relaxation caused by isoproterenol by activation of the Na-K-ATPase was also decreased by the Ca2+-channel antagonists, verapamil and diltiazem. The results suggest 1) Na-K ATPase activity modulates relaxation caused by isoproterenol, prostaglandin E2, and forskolin in canine tracheal smooth muscle, 2) isoproterenol or activation of the Na-K ATPase may cause relaxation partly by reducing Ca2+ influx through potential-dependent Ca2+ channels, and 3) the differences in the inhibitory effects of isoproterenol and Na-K ATPase activity on muscles contracted by acetylcholine and 5-hydroxytryptamine could be due to differences between these contractile agents in their dependence on extracellular Ca2+ for activation.

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