Pharmacological Evidence for a Functional Serotonin-2B Receptor in a Human Uterine Smooth Muscle Cell Line

Abstract

The present study investigated the serotonin-induced increase in phosphoinositide hydrolysis and mobilization of intracellular Ca 2ϩ ([Ca 2ϩ ] i ) in human uterine smooth muscle cells (HUSMCs) to identify the serotonergic receptor positively coupled to phospholipase C in these cells. In phosphoinositide (PI) assays, serotonin (5-HT) and ␣-methyl-5-HT were potent, full agonists (EC 50 ϭ 20 and 4.1 nM, respectively), whereas the phenyleth- Serotonin (5-hydroxytryptamine, 5-HT) is known to exert a wide variety of physiological actions through its interaction with an extensive family of 5-HT cell surface receptors (Hoyer et al., 1994(Hoyer et al., , 2002. In particular, the 5-HT 2 receptor family comprises three subtypes, 5-HT 2A , 5-HT 2B , and 5-HT 2C , which have been reported to play a major role in a host of central nervous system functions including anxiety, depression, migraine, obesity, and schizophrenia. Due to the involvement of 5-HT 2 receptor signaling in these disorders, there has been an increased interest in the therapeutic potential of selective 5-HT 2 ligands as antidepressants, antiobesity drugs, and anxiolytic agents (Hoyer et al., 1994;. Further studies have identified serotonin in human aqueous humor (Veglio et al., 1998) and functionally coupled 5-HT 2 receptors in rat retinal pigment epithelial cells (Osborne et al., 1993) and bovine ciliary epithelium (Inoue-Matsuhisa et al., 2003).These findings suggested a possible role of serotonin and its receptors in aqueous humor dynamics and as a possible target for ocular pathologies. Indeed, it has recently been shown that topical ocular administration of 5-HT 2 receptor agonists effectively lowered intraocular pressure in a nonhuman primate model of laser-induced ocular hypertension (May et al., 2003), suggesting a potential utility of 5-HT 2 agonists as antiglaucoma therapeutics. However, the current lack of subtype-selective ligands, especially agonists, has made it difficult to ascribe the hypotensive action of these molecules to an individual 5-HT 2 receptor subtype.Recently, the appetite suppressant fenfluramine was withArticle, publication date, and citation information can be found at

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

“…The 5-HT 2B receptor has been examined in human uterine smooth muscle cells and agonists increase phosphoinositide hydrolysis, which may lead to smooth muscle cell contraction (Kelly and Sharif, 2006). Serotonin produces relaxation of the porcine oviduct (Inoue et al, 2003) and inhibits myometrial contractility (Kitazawa et al, 1998), a finding somewhat at odds with the data above.…”

Polymorphic variants of the serotonin receptor, 5-HT1A, and the serotonin transporter, 5-HTTLPR, and adverse pregnancy outcomes: A pilot study

“…DNA was prepared from white blood cells by standard salt extraction techniques and subsequently stored at À4 8C for batched analysis. 18 The primers used in the PCR amplification for the C(À1019)G polymorphism in the promoter region of the 5-HT 1A receptor gene were:…”

Human Non-Pigmented Ciliary Epithelium Bradykinin B2-Receptors: Receptor Localization, Pharmacological Characterization of Intracellular Ca2+Mobilization, and Prostaglandin Secretion

“…Based on the relative affinity of BK and its close analogs determined in competition receptor binding experiments in a variety of cells and tissues 11,12,40 and the ability of these peptides to stimulate the production of inositol phosphates in h-TM 10 and in human corneal epithelial 11,20 and other cells, 41 we selected an appropriate range of concentrations of these agents for the [Ca 2+ ] i mobilization [42][43][44] experiments. [Ca 2+ ] i mobilization induced by various peptides in p-h-NPCE and im h-NPCE cells, and to a limited extent in isolated primary human ciliary muscle (h-CM), primary human trabecular meshwork (h-TM) and Chinese hamster ovary cells expressing the full length human cloned B 2 -receptor (CHO-B2; Euroscreen Inc., Gosselies, Belgium), was studied using a Fluorescence Imaging Plate Reader (FLIPR-Tetra; Molecular Devices, Menlo Parl, CA) instrument as previously described.…”