Involvement of cyclooxygenase-dependent pathway in contraction of isolated ileum by urotensin II

Horie, Syunji; Tsurumaki, Yuumi; Someya, Akiyoshi; Hirabayashi, Tetsuya; Saito, Takeshi; Okuma, Yasunobu; Nomura, Yasuyuki; Murayama, Toshihiko

doi:10.1016/j.peptides.2004.09.009

Cited by 10 publications

(6 citation statements)

References 42 publications

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“…Contractile agents such as acetylcholine, histamine and KCl cause a biphasic contractile response consisting of a transient contraction (phasic) followed by a sustained one (tonic) maintained during exposure to the contractile agent (Horie et al, 2005;Tanahashi et al, 2009). It has been reported that the phasic contraction is caused by inositol 1,4,5-trisphosphate (IP 3 )-mediated Ca 2+ release from intracellular stores (Abdel-Latif, 1989;Kobayashi et al, 1989), whereas the tonic contraction is attributed to a Ca 2+ influx through Ca V (Jim et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K + channel activation and decrease in cytosolic calcium concentration

Vasconcelos

Correia

Souza

et al. 2015

European Journal of Pharmacology

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Flavonoid galetin 3,6-dimethyl ether (FGAL) has been isolated from the aerial parts of Piptadenia stipulaceae and has shown a spasmolytic effect in guinea pig ileum. Thus, we aimed to characterize its relaxant mechanism of action. FGAL exhibited a higher relaxant effect on ileum pre-contracted by histamine (EC50=1.9±0.4×10(-7) M) than by KCl (EC50=2.6±0.5×10(-6) M) or carbachol (EC50=1.8±0.4×10(-6) M). The flavonoid inhibited the cumulative contractions to histamine, as well as to CaCl2 in depolarizing medium nominally Ca(2+)-free. The flavonoid relaxed the ileum pre-contracted by S-(-)-Bay K8644 (EC50=9.5±1.9×10(-6) M) but less potently pre-contracted by KCl or histamine. CsCl attenuated the relaxant effect of FGAL (EC50=1.1±0.3×10(-6) M), but apamin or tetraethylammonium (1mM) had no effect (EC50=2.6±0.2×10(-7) and 1.6±0.3×10(-7) M, respectively), ruling out the involvement of small and big conductance Ca(2+)-activated K(+) channels (SKCa and BKCa, respectively). Either 4-aminopyridine or glibenclamide attenuated the relaxant effect of FGAL (EC50=1.8±0.2×10(-6) and 1.5±0.5×10(-6) M, respectively), indicating the involvement of voltage- and ATP-sensitive K(+) channels (KV and KATP, respectively). FGAL did not alter the viability of intestinal myocytes in the MTT assay and decreased (88%) Fluo-4 fluorescence, indicating a decrease in cytosolic Ca(2+) concentration. Therefore, the relaxant mechanism of FGAL involves pseudo-irreversible noncompetitive antagonism of histaminergic receptors, KV and KATP activation and blockade of CaV1, thus leading to a reduction in cytosolic Ca(2+) levels.

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Section: Discussionmentioning

confidence: 99%

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K + channel activation and decrease in cytosolic calcium concentration

Vasconcelos

Correia

Souza

et al. 2015

European Journal of Pharmacology

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“…The ileal smooth muscle is known to present biphasic contraction where, in the first phase, the muscle exhibits a fast and transient contraction followed by a long-lasting second phase characterized by the maintained tonic contraction (Horie et al, 2005;Tanahashi et al, 2009). However, both phasic and tonic antagonist-induced contractions depend on extracellular calcium since both are inhibited in its absence (Honda et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K+ and Ca2+ channels to reduce cytosolic calcium concentration on guinea pig ileum

Santos

Martins

Travassos

et al. 2012

European Journal of Pharmacology

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In this study we investigated the mechanism underlying the spasmolytic action of ent-7α-acetoxytrachyloban-18-oic acid (trachylobane-360) and ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5±0.9 and 4.4±0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl(2)-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca(v)). The Ca(v) participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC(50)=3.5±0.7×10-(5) and 1.1±0.2×10-(5)M) and KCl (EC(50)=5.5±0.3×10-(5) and 1.4±0.2×10-(5)M). K(+) channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5mM tetraethylammonium (TEA(+)) (EC(50)=0.5±0.04×10-(4) and 2.0±0.5×10-(5)M). ATP-sensitive K(+) channel (K(ATP)), voltage activated K(+) channels (K(V)), small conductance calcium-activated K(+) channels (SK(Ca)) or big conductance calcium-activated K(+) channels (BK(Ca)) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K(ATP), K(V) and SK(Ca) (EC(50)=1.1±0.3×10-(5), 0.7±0.2×10-(5) and 0.7±0.2×10-(5)M), but not BK(Ca). A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca(2+)](c)) induced by both trachylobanes in ileal myocytes. In conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K(+) channel positive modulation and Ca(2+) channel blockade, which results in [Ca(2+)](c) reduction at cellular level leading to smooth muscle relaxation.

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“…UII provokes concentration-dependent contractions of guinea pig ileal segments via activation of ganglionic cholinergic neurons (Horie et al, 2003). The contractile response is blocked by cyclooxygenase and phospholipase A 2 inhibitors (Horie et al, 2005), indicating that the effect of UII on myenteric neurons is mediated through prostaglandin biosynthesis. Moreover, UII potently relaxes the mouse anococcygeus muscle (Gibson et al, 1984), suggesting that UII may play a role in the control of defecation.…”

Section: Effect Of Urotensin Ii/urotensin Ii-related Peptide On Thmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

et al. 2014

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Involvement of cyclooxygenase-dependent pathway in contraction of isolated ileum by urotensin II

Cited by 10 publications

References 42 publications

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K + channel activation and decrease in cytosolic calcium concentration

Flavonoid galetin 3,6-dimethyl ether attenuates guinea pig ileum contraction through K + channel activation and decrease in cytosolic calcium concentration

Ent-7α-acetoxytrachyloban-18-oic acid and ent-7α-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K+ and Ca2+ channels to reduce cytosolic calcium concentration on guinea pig ileum

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

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