A new wave of serotonin receptors

doi:10.1016/0959-4388(93)90122-F

Current Opinion in Neurobiology

Volume 3, Issue 3, June 1993, Pages 310-315

https://doi.org/10.1016/0959-4388(93)90122-F Get rights and content

Abstract

The neurotransmitter serotonin mediates diverse effects through multiple receptor subtypes. Recently, many of these receptor subtypes have been identified, molecularly cloned and characterized, advancing our understanding of their functional roles in the central and peripheral nervous systems.

References (56)

J. Peters et al.
Recent Advances in the Electrophysiological Characterization of 5-HT₃ Receptors
Trends Pharmacol Sci
(1992)
B. Costall et al.
The Psychopharmacology of 5-HT₃Receptors
Pharmac Ther
(1990)
J. Yakel et al.
5-HT₃ Receptors Mediate Rapid Responses in Cultured Hippocampus and a Clonal Cell Line
Neuron
(1988)
S. Sugita et al.
5-hydroxytryptamine Is a Fast Excitatory Transmitter at 5-HT₃ Receptors in Rat Amygdala
Neuron
(1992)
C. Waeber et al.
Localisation by Autoradiography of Neuronal 5-HT₃ Receptors in the Mouse CNS
Eur J Pharmacol
(1988)
G. Kilpatrick et al.
The Distribution of Specific Binding of the 5-HT₃ Receptor Ligand [3H]GR65630 in Rat Brain Using Quantitative Autoradiography
Neurosci Lett
(1988)
A.V. Maricq et al.
Primary Structure and Functional Expression of the 5HT₃ Receptor, a Serotonin-gated Ion Channel
Science
(1991)
S. Peroutka et al.
Multiple Serotonin Receptors: Differential Binding of ³H-5-hydroxytryptamine, ³H-lysergic Acid Diethylamide and ³H-spiroperidol
Mol Pharmacol
(1979)
N. Pedigo et al.
Discrimination of Multiple [3H]5-HT Binding Sites by the Neuroleptic Spiperone in Rat Brain
J Neurochem
(1981)
M. Voight et al.
Molecular Cloning and Characterization of a Rat Brain cDNA Encoding a 5-hydroxytryptamine_1B Receptor
EMBO J
(1991)

N. Adham et al.

The Rat 5-hydroxytryptamine_1B Receptor Is the Species Homologue of the Human 5-hydroxytryptamine_1Dβ Receptor

Mol Pharmacol

(1992)

H. Jin et al.

Characterization of the Human 5-hydroxytryptaminelB Receptor

J Biol Chem

(1992)

S.A. Veldman et al.

Cloning and Pharmacological Characterization of a Novel Human 5-hydroxytryptamine]D Receptor Subtype

Mol Pharmacol

(1992)

D. Mochizuki et al.

Cloning and Expression of the Human 5-HTIB-type Receptor Gene

Biochem Biopbys Res Commun

(1992)

S. Suryanarayana et al.

A Point Mutation in the Seventh Hydrophobic Domain of the a2-Adrenergic Receptor Increases its Affinity for a Family of β-receptor Antagonists

J Biol Chem

(1991)

D. Oksenberg et al.

A Single Amino-acid Difference Confers Major Pharmacological Variation between Human and Rodent 5-HT_IB Receptors

Nature

(1992)

M.A. Metcalf et al.

Conversion of the Human 5-HT_1Dβ Serotonin Receptor to the Rat 5-HTIB Ligand-binding Phenotype by THR³⁵⁵ASN Site Directed Mutagenesis

Biochem Pharmacol

(1992)

G. McAllister et al.

Molecular Cloning of a Serotonin Receptor from Human Brain (5HT_1E): A Fifth 5HT₁-like Subtype

N. Adham et al.

Cloning of Another Human Serotonin Receptor (5 HTIF): A Fifth 5-HTI Receptor Subtype Coupled to the Inhibition of Adenylate Cyclase

A. Katz et al.

Subunits R7 of Heterotrimeric G Protein Activate β₂ Isoform of Phospholipase C

Nature

(1992)

D. Julius

Molecular Biology of Serotonin Receptors

Annu Rev Neurosci

(1991)

S.J. Peroutka

5-Hydroxytryptamine Receptors

J Neurochem

(1993)

V. Derkach et al.

5-HT3 Receptors Are Membrane Ion Channels

Nature

(1989)

J. Yang et al.

5-HT₃ Receptor Channels in Dissociated Rat Superior Cervical Ganglion Neurones

J Physiol (Lond)

(1992)

B. Richardson et al.

The Pharmacology, Distribution and Function of 5-HT₃ Receptors

G.J. Kilpatrick et al.

Identification and Distribution of 5-HT₃ Receptors in Rat Brain Using Radioligand Binding

N. Ropert et al.

Serotonin Facilitates GABAergic Transmission in the CA1 Region of Rat Hippocampus in vitro

J Pbysiol (Lond)

(1991)

K. Bunce et al.

Clinical Evaluation of 5-HT3 Receptor Antagonists as Anti-emetics

Trends Pharmacol Sci

(1991)

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Citation Excerpt :
Neuronal nicotinic acetylcholine receptors (nAChRs) are important receptors involved in many functional processes such as cognition, learning, and memory (Broide and Leslie, 1999; Levin and Simon, 1998; Paterson and Nordberg, 2000; Role and Berg, 1996). The nAChRs belong to a superfamily of ligand-gated ion channels such as GABA, glycine, and 5-HT3 serotonin receptors (Béchade et al., 1994; Bormann and Feigenspan, 1995; Corringer et al., 2000; Karlin, 2002; Macdonald and Olsen, 1994; Tecott and Julius, 1993). The nAChRs in mammals are divided into two subtypes, including muscle type and neuronal type (Lindstrom, 2000).
Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the peripheral blood mononuclear cells of rhesus macaques
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To find out whether rhesus macaque peripheral blood mononuclear cells (PBMCs) express mRNA for 5-HT receptors, blood samples from normal healthy rhesus monkeys were used to isolate PBMCs by Ficoll-paque density gradient centrifugation. Total RNA was extracted from MT-2 cells, Hut-78 cells, naive or phytohemagglutinin (PHA) stimulated human and monkey PBMCs. One tube RT-PCR was performed using primers specific for human 5-HT1_A, 5-HT1_B, 5-HT1_E, 5-HT2_A, 5-HT2_B, 5-HT2_C, 5-HT3, 5-HT4, 5-HT6, and 5-HT7 receptors. Amplicons of expected sizes were obtained from human cell lines as well as both human and monkey PBMCs. Both PHA stimulated human and monkey PBMCs express mRNAs for 5-HT1_A, 5-HT1_B, 5-HT1_E, 5-HT2_A, 5-HT3, 5-HT4, 5-HT6 receptor types/subtypes. However, mRNAs for 5-HT1_B, 5-HT1_E and 5-HT2_A cannot be confidently detected in some of the PBMC samples without PHA stimulation. 5-HT2_B and 5-HT7 receptor mRNA was not detected in most of the samples and 5-HT2_C receptor mNRA was not detected at all. FACS analysis revealed that CD3+ lymphocyte increased more than 20% among lymphocytes in the PHA stimulated PBMCs. These data indicate that similar to human PBMC, rhesus macaque PBMC may express multiple types of 5-HT receptors and the expression profile could change after PHA stimulation due to either the changes in cell composition or changes in gene transcription level. This provided a basis for further studies on the neuroimmunomodulatory interactions of 5-HT in rhesus macaques.
Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor
2004, Physiology and Behavior
Citation Excerpt :
Only 5-HT-3A receptor can form homomeric channels on its own [1], and this subunit is essential for the expression of functional 5-HT-3 receptor complexes [3]. The localization of the 5-HT-3A receptor in limbic regions, such as cortex, amygdala, bed nucleus of the stria terminalis, and hippocampal formation [4–9], suggests its involvement in anxiety, cognition, and hypothalamic–pituitary–adrenal (HPA) function. However, the exact role of the 5-HT-3A receptor in anxiety-related behaviors has been difficult to determine, and the role of this receptor in regulation of HPA activity is largely unexplored.
The serotonin-3 (5-HT-3A) receptor has been localized in limbic and brainstem structures that regulate anxiety-related behavior and hypothalamic–pituitary–adrenal (HPA) activity, but its role in regulating anxiety-related behaviors is equivocal, and evidence for its role in regulating HPA activity is limited. Therefore, we used 5-HT-3A receptor knockout (KO) mice to further study these issues. Behavior in the elevated plus maze, open field, light–dark box and after Pavlovian fear conditioning was examined in addition to HPA activity under basal and acute stress conditions. Compared to age-matched adult male wild-type (WT) controls, adult male KO mice exhibited increased distance traveled in the open arms of the elevated plus maze, consistent with decreased measures of anxiety. There were no differences between the two genotypes in exploratory behavior in the open field or light–dark test. KO mice displayed enhanced fear conditioning indexed by fear-induced freezing behavior. KO mice displayed lower adrenocorticotropin (ACTH) responses to restraint or lipopolysaccharide (LPS). In addition, lower vasopressin mRNA in the paraventricular nucleus of the hypothalamus (PVN) and higher corticotropin-releasing hormone (CRH) mRNA in the central amygdala were observed in KO compared to WT mice. Therefore, deletion of the 5-HT-3A receptor revealed an important role for this receptor in regulating HPA responses to acute stress and a potential interaction between the 5-HT-3A receptor and CRH in the amygdala. Together, these data suggest that the 5-HT-3A receptor does not have a unitary role in the regulation of anxiety- and fear-related behaviors but has a potentially substantial role in the regulation of HPA activity.
Neuroactive steroids: Mechanisms of action and neuropsychopharmacological properties
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Steroids influence neuronal function through binding to cognate intracellular receptors which may act as transcription factors in the regulation of gene expression. In addition, certain so-called neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially distinct 3α-reduced metabolites of progesterone and deoxycorticosterone are potent positive allosteric modulators of γ-aminobutyric acid type A (GABA_A) receptors. However, also classical steroid hormones such as 17β-estradiol, testosterone and progesterone are neuroactive steroids because they may act as functional antagonists at the 5-hydroxytryptamine type 3 (5-HT₃) receptor, a ligand-gated ion channel or distinct glutamate receptors. A structure–activity relationship for the actions of a variety of steroids at the 5-HT₃ receptor was elaborated that differed considerably from that known for GABA_A receptors. Although a bindings site for steroids at GABA_A receptors is still a matter of debate, meanwhile there is also evidence that steroids interact allosterically with ligand-gated ion channels at the receptor membrane interface. On the other hand, also 3α-reduced neuroactive steroids may regulate gene expression via the progesterone receptor after intracellular oxidation into 5α-pregnane steroids. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose-dependent fashion in male Wistar rats. Moreover, progesterone and 3α-reduced neuroactive steroids produce a benzodiazepine-like sleep EEG profile in rats and humans. During major depression, there is a disequilibrium of such 3α-reduced neuroactive steroids which is corrected by successful treatment with antidepressant drugs. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. Studies in patients with panic disorder suggest that neuroactive steroids may also play a role in modulating human anxiety. Both the genomic and non-genomic effects of steroids in the brain may contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may represent a new treatment strategy for neuropsychiatric disorders.
The role of neuronal nicotinic acetylcholine receptor subunits in autonomic ganglia: Lessons from knockout mice
2002, Progress in Neurobiology
Neuronal nicotinic acetylcholine receptors (nAChR), composed of 12 subunits (α2–α10, β2–β4), are expressed in autonomic ganglia, playing a central role in autonomic transmission. The repertoire of nicotinic subunits in autonomic ganglia includes α3, α5, α7, β2 and β4 subunits. In the last 10 years, heterologous expression studies have revealed much about the nature of neuronal nAChRs. However, there is only limited understanding of subunit actions in autonomic system. Functional deletions of subunit by gene knockout in animals could overcome these limitations. We review recent studies on nAChRs on autonomic ganglia for physiological and pharmacological properties and potential locations of the subunits.
Chapter 1 The cerebellum: chemoarchitecture and anatomy
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This chapter reviews the external and internal morphology of the cerebellum. It focuses on the afferent and intrinsic connections of the cerebellum. Three layers are present in the cortex. The granular layer borders on the central white matter of the cerebellum. The Purkinje cell layer contains the cell bodies of the Purkinje cells, which are arranged in a single row. The perikarya of the Bergmann glia (the Golgi epithelial cells) are intercalated between the larger Purkinje cells. The molecular layer has a low cell content. It contains the dendritic arbors of the Purkinje cells and the Bergmann glial fibers, which run up to the pial surface where they constitute the external glial limiting membrane. Granule cells are small neurons located in cell nests in the granular layer. Cell-free spaces in the granular layer, which are known as the “protoplasmatic islands of Held,” contain the terminals of the mossy fibers.

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A new wave of serotonin receptors

Abstract

Trends Pharmacol Sci

Pharmac Ther

Neuron

Neuron

Eur J Pharmacol

Neurosci Lett

Science

Mol Pharmacol

J Neurochem

EMBO J

Mol Pharmacol

J Biol Chem

Mol Pharmacol

Biochem Biopbys Res Commun

J Biol Chem

Nature

Biochem Pharmacol

Nature

Molecular Biology of Serotonin Receptors

Annu Rev Neurosci

5-Hydroxytryptamine Receptors

J Neurochem

5-HT3 Receptors Are Membrane Ion Channels

Nature

5-HT3 Receptor Channels in Dissociated Rat Superior Cervical Ganglion Neurones

J Physiol (Lond)

The Pharmacology, Distribution and Function of 5-HT3 Receptors

Identification and Distribution of 5-HT3 Receptors in Rat Brain Using Radioligand Binding

Serotonin Facilitates GABAergic Transmission in the CA1 Region of Rat Hippocampus in vitro

J Pbysiol (Lond)

Clinical Evaluation of 5-HT3 Receptor Antagonists as Anti-emetics

Trends Pharmacol Sci

5-HT₃ Receptor Channels in Dissociated Rat Superior Cervical Ganglion Neurones

The Pharmacology, Distribution and Function of 5-HT₃ Receptors

Identification and Distribution of 5-HT₃ Receptors in Rat Brain Using Radioligand Binding