Distribution of 5-ht5A, 5-ht5B, 5-ht6 and 5-HT7 receptor mRNAs in the rat brain

Kinsey, Anna; Wainwright, Anna; Heavens, R.P.; Sirinathsinghji, D.J.S.; Oliver, Kevin R.

doi:10.1016/s0169-328x(01)00034-1

Cited by 84 publications

(63 citation statements)

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“…Evidence that the 5-HT 5A receptor mediates an unidentified 5-HT current in cortex The 5-HT 5A receptor is found in the rodent cerebral cortex (Grailhe et al, 1999;Kinsey et al, 2001) and expressed preferentially in layer V neurons (Belgard et al, 2011), together with the more extensively studied 5-HT 1A and 5-HT 2 receptors. To examine the 5-HT 5A receptor current, the latter receptors were blocked with 10 -30 nM WAY-100635 and 1-2 M ketanserin; higher concentrations were used for rapid blockade (10 min), followed by continued application of the lower concentrations.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, the 5-HT 5A receptor and 5-HT 1A receptor display similar coupling to effectors (for 5-HT 1A , see Raymond et al, 1999; for 5-HT 5A , see Grailhe et al, 2001; present study) and efficacy for the 5-HT ligand (for 5-HT 1A , see Okuhara and Beck, 1998; for 5-HT 5A , see present study). Moreover, like the 5-HT 1A receptor, the 5-HT 5A receptor is expressed in a number of limbic regions, including the hippocampus and cortex (Grailhe et al, 1999;Kinsey et al, 2001). Despite these similarities, the 5-HT 5A knock-out mice do not display the anxiety phenotype observed in 5-HT 1A knock-out mice (Ramboz et al, 1998), but rather exhibit altered LSD-mediated explorative behaviors (Grailhe et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The 5-HT 5A receptor subtype is the least understood, despite its widespread expression in the human and rodent brains (Pasqualetti et al, 1998;Kinsey et al, 2001). To date, there has been limited functional evidence of the 5-HT 5A receptor in the brain (Sprouse et al, 2004;Thomas et al, 2006), and its endogenous channel effector(s) remain uncertain (Grailhe et al, 2001;Noda et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

Goodfellow

Bailey²,

Lambe³

2012

J. Neurosci.

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The 5-HT 5A receptor is the least understood serotonin (5-HT) receptor. Here, we electrophysiologically identify and characterize a native 5-HT 5A receptor current in acute ex vivo brain slices of adult rodent prefrontal cortex. In the presence of antagonists for the previously characterized 5-HT 1A and 5-HT 2 receptors, a proportion of layer V pyramidal neurons continue to show 5-HT-elicited outward currents in both rats and mice. These 5-HT currents are suppressed by the selective 5-HT 5A antagonist, SB-699551, and are not observed in 5-HT 5A receptor knock-out mice. Further characterization reveals that the 5-HT 5A current is activated by submicromolar concentrations of 5-HT, is inwardly rectifying with a reversal potential near the equilibrium potential for K ϩ ions, and is suppressed by blockers of Kir3 channels. Finally, we observe that genetic deletion of the inhibitory 5-HT 5A receptor results in an unexpected, large increase in the inhibitory 5-HT 1A receptor currents. The presence of functional prefrontal 5-HT 5A receptors in normal rodents along with compensatory plasticity in 5-HT 5A receptor knock-out mice testifies to the significance of this receptor in the healthy prefrontal cortex.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

Goodfellow

Bailey²,

Lambe³

2012

J. Neurosci.

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“…Moreover, considering the limited number of evolutionarily conserved NRSEs, it is noteworthy that a third member of the serotonin signaling system, the serotonin-6 receptor, also contains a potential conserved NRSE (supplemental Table S2). Curiously, genes for both serotonin-1a receptor and serotonin-6 receptor contain classic length (21 bp) NRSEs and are expressed in multiple neuron types (53), whereas TPH2 contains a bNRSE of 27 bp, and its expression in brain is restricted to raphe neurons (2). Possibly REST may play a global role in maturation of the serotonergic system, but the type of NRSE it binds may confer additional cell-type specific gene expression.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Tryptophan Hydroxylase-2 Gene Expression by a Bipartite RE-1 Silencer of Transcription/Neuron restrictive Silencing Factor (REST/NRSF) Binding Motif

Patel

Bochar

Turner

et al. 2007

Journal of Biological Chemistry

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Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in raphe serotonin biosynthesis, and polymorphisms of TPH2 are implicated in vulnerability to psychiatric disorders. Dynamic transcription regulation of TPH2 may underlie differences in vulnerability. We identified a transcription element in the TPH2 promoter that resembles the binding motif for RE-1 silencer of transcription (REST; also known as NRSF) transcription factor. REST limits tissue expression of non-neuronal genes through a canonical 21-bp motif called the NRSE (neuron-restrictive silencing element). The NRSE in TPH2 is a novel bipartite variant interrupted by a 6-base insertion. We confirmed that this bipartite NRSE permits transcriptional repression by REST identical to canonical NRSE in rat C6-glioma cells. Synthetic permutations of the motif revealed considerable flexibility in the juxtaposition of the two halves of bipartite NRSE. Computational analysis revealed many bipartite NRSE variants conserved between mouse and human genomes. A subgroup of these was found to bind REST by chromatin immunoprecipitation. Messenger RNAs for TPH2 and potassium channel H6, another gene with a bipartite NRSE, were up-regulated by dominant-negative REST in C6-glioma cells. These findings, which indicate that TPH2 expression is part of the developmental program regulated by REST and suggest that many previously unrecognized genes may be regulated by REST through the novel motif, have implications for the mechanism of REST action.Serotonin levels are regulated by the rate-limiting enzyme tryptophan hydroxylase, of which a neuronal isoform (NCBI Entrez Gene ID: TPH2) 3 was recently identified (1). TPH2 gene expression in the brain is restricted to raphe neurons, and TPH2 is likely the gene coding for the majority of tryptophan hydroxylase in these cells (1, 2). Serotonin modulates a variety of complex behaviors (3), and its signaling is implicated in the mechanism for a subset of antidepressants (4), but its precise role in mood regulation is unclear. A number of manipulations, including restriction of the essential dietary precursor tryptophan (5), stimulant drugs of abuse (6), or adverse developmental experiences (7), result in low brain serotonin levels and may underlie associated depression or anxiety phenotypes. Functional variants of TPH2 in mice are associated with decreased brain serotonin levels (8), and a TPH2 polymorphism in humans arguably (9) confers vulnerability to major depression (10). Associations with TPH2 polymorphisms are also reported for suicide (11), obsessivecompulsive disorder (12), and attention deficit disorder (13)(14)(15).In contrast to the growing number of genetic association studies, little is known about the regulation of TPH2 expression. Limited studies suggest that TPH2 mRNA levels are decreased following stress corticosteroids (16), unchanged (16) or increased by ovarian steroids (17), and increased by hypotensive stress (18) and one recent report suggests that POU3F2 may regulate TPH2 through a functional single-nucleoti...

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“…The specific distribution of 5-HT 7 receptor mRNA in rat and guinea pig brain is well described Gustafson et al, 1996;Mengod et al, 1996;Kinsey et al, 2001;Neumaier et al, 2001). However, the characterization and study of the anatomical distribution of 5-HT 7 receptor binding sites in brain tissue have been hampered by the lack of a specific radioligand.…”

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confidence: 94%

Reconsideration of 5-Hydroxytryptamine (5-HT)₇Receptor Distribution Using [³H]5-Carboxamidotryptamine and [³H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT_1AKnockout and 5-HT_1A/1BDouble-Knockout Mice

Bonaventure

Nepomuceno²,

Kwok³

et al. 2002

J Pharmacol Exp Ther

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The characterization and anatomical distribution of 5-hydroxytryptamine (5-HT) 7 receptor binding sites in brain tissue has been hampered by the lack of a specific radioligand. In the present autoradiographic study, we took advantage of 5-HT 1A knockout and 5-HT 1A/1B double-knockout mice to revisit the pharmacological characterization and anatomical localization of 5-HT 7 binding sites in mouse brain using [ The 5-HT 7 receptor is the most recently identified member of the family of G protein-coupled 5-HT receptors (for review, see Vanhoenacker et al., 2000). The 5-HT 7 receptor has been cloned from rat Ruat et al., 1993;Shen et al., 1993), mouse (Plassat et al., 1993), human (Bard et al., 1993), and guinea pig (Tsou et al., 1994). The receptor is positively coupled to adenylate cyclase, preferentially via Gs. It exhibits a high degree of interspecies homology (approximately 95%) but a low sequence homology with other 5-HT receptors (Ͻ40%). In rat and human, three different splice variants have been described to date, which are thought to have similar pharmacology and function (Heidmann et al., 1997;Krobert et al., 2001). The pharmacological profile of the 5-HT 7 receptor is consistent across all tested species and is characterized by high affinity for the 5-HT 1 agonists 5-CT, 5-HT, and 8-OH-DPAT; and the 5-HT 2 antagonists ritanserin, metergoline, mesulergine, and risperidone. Possible physiological functions for this receptor have been suggested, including relaxation in several vascular preparations (Bard et al., 1993;Shen et al., 1993) and circadian rhythm control via the suprachiasmatic nucleus of the hypothalamus Gannon, 2001). Because 8-OH-DPAT has been shown to exhibit a relatively high affinity for the 5-HT 7 receptor, multiple functions formerly ABBREVIATIONS:

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Distribution of 5-ht5A, 5-ht5B, 5-ht6 and 5-HT7 receptor mRNAs in the rat brain

Cited by 84 publications

References 21 publications

The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

Regulation of Tryptophan Hydroxylase-2 Gene Expression by a Bipartite RE-1 Silencer of Transcription/Neuron restrictive Silencing Factor (REST/NRSF) Binding Motif

Reconsideration of 5-Hydroxytryptamine (5-HT)₇Receptor Distribution Using [³H]5-Carboxamidotryptamine and [³H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT_1AKnockout and 5-HT_1A/1BDouble-Knockout Mice

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Distribution of 5-ht5A, 5-ht5B, 5-ht6 and 5-HT7 receptor mRNAs in the rat brain

Cited by 84 publications

References 21 publications

The Native Serotonin 5-HT5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

The Native Serotonin 5-HT5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

Regulation of Tryptophan Hydroxylase-2 Gene Expression by a Bipartite RE-1 Silencer of Transcription/Neuron restrictive Silencing Factor (REST/NRSF) Binding Motif

Reconsideration of 5-Hydroxytryptamine (5-HT)7Receptor Distribution Using [3H]5-Carboxamidotryptamine and [3H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT1AKnockout and 5-HT1A/1BDouble-Knockout Mice

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The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

The Native Serotonin 5-HT_5AReceptor: Electrophysiological Characterization in Rodent Cortex and 5-HT_1A-Mediated Compensatory Plasticity in the Knock-Out Mouse

Reconsideration of 5-Hydroxytryptamine (5-HT)₇Receptor Distribution Using [³H]5-Carboxamidotryptamine and [³H]8-Hydroxy-2-(di-n-propylamino)tetraline: Analysis in Brain of 5-HT_1AKnockout and 5-HT_1A/1BDouble-Knockout Mice