Evaluation of Serotonin Levels in Human Aqueous Humor

Veglio, Franco; Sanctis, Ugo de; Schiavone, D.; Cavallone, S; Mulatero, Paolo; Grignolo, Fm; Chiandussi, L

doi:10.1159/000027268

Cited by 22 publications

(13 citation statements)

References 6 publications

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“…Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al, 1998) and other mammals (Boerrigter et al, 1992). These observations have generated considerable interest in the role that serotonin might have in aqueous humor dynamics and even whether 5-HT might be involved in the development of ocular hypertension and glaucoma.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

May¹,

McLaughlin²,

Sharif³

et al. 2003

J Pharmacol Exp Ther

106

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Published investigations of serotonin-1A (5-hydroxytryptamine 1A ; 5-HT 1A ) receptor agonists and serotonin-2A (5-hydroxytryptamine 2A ; 5-HT 2A ) receptor antagonists in nonprimate species provide conflicting results with regard to their intraocular pressurelowering efficacy. Thus, their therapeutic utility in the treatment of human glaucoma has been confusing. We evaluated the effect of selected 5-HT 1A agonists and 5-HT 2A receptor antagonists on intraocular pressure in a nonhuman primate model, the conscious cynomolgus monkey with laser-induced ocular hypertension. Neither selective 5-HT 1A agonists [e.g., R-8-hydroxy-2-(di-n-propylamino)tetralin and flesinoxan] nor selective 5-HT 2 receptor antagonists [e.g.,pressure in the primate model following topical ocular administration. However, compounds that function as agonists at both the 5-HT 1A and 5-HT 2 receptors were found to effectively lower intraocular pressure in the model: 5-hydroxy-␣-methyltryptamine, 5-methoxy-␣-methyltryptamine, 5-hydroxy-N,N-dimethyltryptamine (bufotenine), and 5-methoxy-N,N-dimethyltryptamine. Furthermore, the selective 5-HT 2 receptor agonist R-(Ϫ)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane lowered intraocular pressure in the primate model, demonstrating a pharmacological response associated with activation of the 5-HT 2 receptor. These observations suggest that compounds that function as efficient agonists at 5-HT 2 receptors should be considered as potential agents for the control of intraocular pressure in the treatment of ocular hypertension and glaucoma in humans.Identification of several of the numerous serotonin receptors in ocular tissues of the anterior segment of the eye, including the iris-ciliary body of rabbit (Chidlow et al., 1998) and human (Martin et al., 1992), suggests that this neurotransmitter may play an important role in the regulation of intraocular pressure (IOP). Serotonin (5-hydroxytryptamine; 5-HT) is also found in the aqueous humor of humans (Veglio et al., 1998) and other mammals (Boerrigter et al., 1992). These observations have generated considerable interest in the role that serotonin might have in aqueous humor dynamics and even whether 5-HT might be involved in the development of ocular hypertension and glaucoma. There have been numerous conflicting reports on the effect of 5-HT and various 5-HT receptor ligands on IOP in the rabbit, dog, and humans. These observed differences in IOP response may be due to species differences, route of administration, or the lack of 5-HT receptor selectivity of the agents evaluated. For example, 5-HT has been shown to lower IOP in rabbits following intravenous injection (Chiang, 1974). However, when injected intracamerally in the rabbit, a rise in IOP was observed (Krootila et al., 1987). Furthermore, topical ocular administration of 5-HT to the rabbit was reported to result in either a decrease (Krootila et al., 1987) or an increase (Meyer-Bothling et al., 1993) in IOP.Article, publication date, and citation information can be found at

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Section: Introductionmentioning

confidence: 99%

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

May¹,

McLaughlin²,

Sharif³

et al. 2003

J Pharmacol Exp Ther

106

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“…5-HT has been detected biochemically in the iris-ciliary body and aqueous humour of a number of species, including rabbits and humans [16,17,19,24,26], and putative serotonergic nerve fibres have also been reported in the rabbit iris-ciliary body [24].…”

Section: Introductionmentioning

confidence: 99%

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

Chidlow

Hiscott

Osborne

2004

Graefe's Arch Clin Exp Ophthalmol

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“…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.…”

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confidence: 99%

mentioning

confidence: 99%

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

Kelly¹,

Sharif²

2006

J Pharmacol Exp Ther

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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

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Evaluation of Serotonin Levels in Human Aqueous Humor

Cited by 22 publications

References 6 publications

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

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

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Evaluation of Serotonin Levels in Human Aqueous Humor

Cited by 22 publications

References 6 publications

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT1A and 5-HT2 Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Expression of serotonin receptor mRNAs in human ciliary body: a polymerase chain reaction study

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

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Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys

Evaluation of the Ocular Hypotensive Response of Serotonin 5-HT_1A and 5-HT₂ Receptor Ligands in Conscious Ocular Hypertensive Cynomolgus Monkeys