title: 5-hydroxytryptamine and its receptors in systemic vascular walls.
abstract: 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.
authors.affiliation: Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido.
authors.forename: Takuji
authors.initials: T
authors.lastname: Machida
authors.forename: Kenji
authors.initials: K
authors.lastname: Iizuka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirafuji
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin