5-Hydroxytryptaime induces cyclooxygenase-2 in rat vascular smooth muscle cells: Mechanisms involving Src, PKC and MAPK activation

Machida, Takuji; Ohta, Misa; Onoguchi, Akina; Iizuka, Kenji; Sakai, Masaaki; Minami, Masaru; Hirafuji, Masahiko

doi:10.1016/j.ejphar.2010.12.044

Cited by 24 publications

(21 citation statements)

References 27 publications

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“…Again, these reports suggest that selective inhibition of the 5-HT 2A receptor indirectly enhances the actions of 5-HT 1B receptors in ECs, possibly resulting in an increase in NO production and a vasodilator response. Considering that sarpogrelate inhibits 5-HT-induced iNOS suppression in VSMCs 10,11) as mentioned above, sarpogrelate may have the potential to increase NO production via both eNOS in ECs and iNOS in VSMCs.…”

Section: Direct and Indirect Actions Of Sarpo-grelate On Vascular Smomentioning

confidence: 96%

“…The PKC signaling pathway by 5-HT 2A receptor activation also inhibits IL-1β-induced NO production and inducible NOS (iNOS) expression. 10,11) 5-HT 2A receptor stimulation also affects the arachidonate cascade in VSMCs. We have reported that 5-HT induces vasodilating prostaglandin I 2 (PGI 2 ) and cyclooxygenase-2 (COX-2) expression via Src, PKC and mitogen-activated protein kinase (MAPK) activation.…”

Section: Function and Signaling Mechanisms In Vascular Smooth Muscle mentioning

confidence: 99%

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5-Hydroxytryptamine and Its Receptors in Systemic Vascular Walls

Machida

Iizuka

Hirafuji

2013

Biological & Pharmaceutical Bulletin

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5-hydroxytryptamine (5-HT) in the bloodstream is largely contained in platelets and circulates throughout the entire vascular system. 5-HT released from activated platelets dramatically changes the function of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). In VSMCs, 5-HT induces proliferation and migration via 5-HT2A receptors. These effects are further enhanced by vasoactive substances such as thromboxane A2 and angiotensin II. 5-HT2A receptor activation in VSMCs also causes both enhancement of prostaglandin I2 production by inducing cyclooxygenase-2 and reduction of nitric oxide (NO) by suppressing inducible NO synthase. Evidence showing that 5-HT in ECs plays a principal role in angiogenesis now exists. Stimulation of 5-HT1 and/or 5-HT2 receptors has been implicated in the angiogenic effect of 5-HT. The extracellular signal-regulated kinase and endothelial NO synthase (eNOS) activation-dependent pathways are involved in the mechanisms. Moreover, 5-HT4 receptors in ECs have been shown to also regulate angiogenesis. Recent reports show sarpogrelate, a selective antagonist of the 5-HT2A receptor, indirectly enhances the function of 5-HT1B receptors in ECs via inhibition of 5-HT2A receptors in VSMCs or platelets. This indirect action of 5-HT1B receptors in ECs may increase NO production derived from eNOS and a vasodilator response. Furthermore, sarpogrelate and other 5-HT2A receptor antagonists have been shown to reduce the constitutive activity of 5-HT2A receptors. It is believed that increasing evidence on the role of 5-HT receptors will contribute to the expansion of the clinical application of existing therapeutic drugs such as sarpogrelate, and to the development of new 5-HT receptor-related drugs for treating cardiovascular diseases.

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Section: Direct and Indirect Actions Of Sarpo-grelate On Vascular Smomentioning

confidence: 96%

Section: Function and Signaling Mechanisms In Vascular Smooth Muscle mentioning

confidence: 99%

5-Hydroxytryptamine and Its Receptors in Systemic Vascular Walls

Machida

Iizuka

Hirafuji

2013

Biological & Pharmaceutical Bulletin

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“…Three principal MAPKs are expressed in various tissues (p42/44, JNK, and p38 MAPK) [26]. Reports are there demonstrating activation of MAP kinase by 5-HT7 receptors in hippocampal neurons [27] and 5-HT induces cyclooxygenase (COX)-2 by acting on MAPK activation in vascular smooth muscle cells [28]. Therefore, 5-HT can regulate the MAPK system.…”

Section: Discussionmentioning

confidence: 99%

5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

Shahi

Choi

Zuo

et al. 2011

Korean J Physiol Pharmacol

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“…Serotonin also potentiates the mitogenic effects of other vasoactive agents, such as endothelin-1, angiotensin II, urotensin II, and thromboxane A 2 (Watanabe et al, 2001c(Watanabe et al, , 2001dPakala et al 1997), platelet-derived microparticles (Pakala, 2004), coagulation factors, such as thrombin and coagulation factor Xa (Pakala & Benedict, 1999;Pakala, 2003), and monocyte chemoattractant protein-1 on VSMCs (Watanabe et al, 2001f). In addition, 5-HT stimulates the expression of interleukin-6 and cyclooxygenase-2 in VSMCs (Ito et al, 2000;Machida et al, 2011).…”

Section: Vsmc Proliferationmentioning

confidence: 99%