The distribution of 5-HT1D and 5-HT1E binding sites in human brain

doi:10.1016/0014-2999(92)90473-H

European Journal of Pharmacology

Volume 222, Issue 1, 3 November 1992, Pages 137-142

https://doi.org/10.1016/0014-2999(92)90473-H Get rights and content

Abstract

Total 5-HT_I, 5-HT_1D and 5-HT_1E binding sites were measured in homogenates of human frontal cortex, hippocampus, amygdala, globus pallidus, caudate and putamen. Combined 5-HT_{$1 D 1 E$} sites were the predominant 5-HTI subtype (66–95% of total 5-HT₁ sites) in all regions except hippocampus (38% of total 5-HTI sites). Globus pallidus contained the highest density and the highest proportion of 5HT_1D sites (74% of total 5-HT₁ sites). 5HT_1D sites in the other brain areas accounted for 19–27% of the total 5-HT₁ sites. The highest densities and the highest proportions of 5-HTIE sites were in caudate (72%) and putamen (64%) and the lowest density and lowest proportion in hippocampus (16%).

References (27)

M.S. Beer et al.
An investigation of the 5-HT_1D receptor binding affinity of 5-HT, 5-CT and sumatriptan in the CNS of seven species
Eur. J. Pharmacol.
(1992)
S.C. Cheetham et al.
Brain 5-HT₂ receptor binding sites in depressed suicide victims
Brain Res.
(1988)
A.M. Galzin et al.
Modulation of 5-HT release by presynaptic inhibitory and facilitatory 5-HT receptor in brain slices
Adv. Biosci.
(1991)
D. Hoyer et al.
Serotonin receptors in human brain. I. Characterization and autoradiographic localization of 5-HTIp recognition sites. Apparent absence of 5-HT_1B recognition sites
Brain Res.
(1986)
D. Hoyer et al.
Serotonin receptors in human brain. II. Characterization and autoradiographic localization of 5-HT_1D and 5-HT₂ recognition sites
Brain Res.
(1986)
O.H. Lowry et al.
Protein measurement with the Folin phenol reagent
J. Biol. Chem.
(1951)
C.O. Mahle et al.
[³H]5-Carboxamidotryptamine labels multiple high affinity 5-HTID-like sites in guinea pig brain
Eur. J. Pharmacol.
(1991)
D.N. Middlemiss et al.
A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea pig frontal cortex
Eur. J. Pharmacol.
(1988)
K.J. Miller et al.
Quantitative autoradiography of 5-CT-sensitive 5-HT_1D and 5-CT-insensitive (5-HTIE) serotonin receptors in human brain
Neurosci. Lett.
(1992)
C. Waeber et al.
Visualization of a novel serotonin recognition site (5-HTID) in the human brain by autoradiography
Neurosci. Lett.
(1988)

A. De Lean et al.

Validation and analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes

Mol. Pharmacol.

(1982)

L.E. Elliott et al.

5-HTID binding sites: possible subpopulations and species differences

A.M. Galzin et al.

Pharmacological characterisation of the serotonin (5-HT) autoreceptor modulating the electrically-evoked release of 3H 5-HT from slices of human frontal cortex membranes

Soc. Neurosci. Abstr.

(1988)

Cited by (29)

Distribution of 5-HT receptors in the central nervous system: an update
2020, Handbook of Behavioral Neuroscience
Citation Excerpt :
The existence of 5-ht1e receptors was first described in the human cortex as the population of [3H]-5-HT binding sites remaining following the blockade of 5-HT1A, 5-HT1B, and 5-HT1D receptors with 100 nM 5-CT and of 5-HT2C receptors with 100 nM mesulergine (Leonhardt, Herrick-Davis, & Titeler, 1989). Subsequent autoradiographic (Miller & Teitler, 1992) and binding studies (Lowther, DePaermentier, Crompton, & Horton, 1992) also in the human brain described the presence of high densities of this receptor in caudate, putamen, medial and lateral globus pallidus, amygdala, frontal cortex, and lower densities in hippocampus. Cloning efforts confirmed the existence in the human genome of a gene coding for a receptor with the characteristics of 5-ht1e binding sites (McAllister et al., 1992; Zgombick et al., 1992); several years later the guinea pig 5-ht1e receptor was also cloned (Bai et al., 2004).
Almost 10 years have passed since we wrote the review on the “Distribution of 5-HT receptors in the central nervous system” in this series (Mengod, Cortés, Vilaró, & Hoyer, 2010). The number of 5-HT receptors remains the same: 14 receptor subtypes grouped in seven families. New findings are related to the identification of the phenotype of the cells expressing 5-HT receptors and their colocalization with other related neurotransmitters and neurotransmitter receptors, some in neurons, others in glial cells or astrocytes (Zhang et al., 2010). The application of immunohistochemistry adds new information about this colocalization. A number of studies are centered on the expression of 5-HT receptors in brain areas related with migraine. New labeled ligands have been developed and preferentially used for positron emission tomography studies in various pathological conditions, as such molecules are considered as potential treatments and/or biomarkers for various diseases.
Binding profile of the novel 5-HT(1B/1D) receptor antagonist,[3H]GR 125,743, in guinea-pig brain: a comparison with [3H]5-carboxamidotryptamine
1997, European Journal of Pharmacology
The antinociceptive potencies of the enantiomorphs of TAN-67 (2-methyl-4aα-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aα-octahydro-quinolino[2,3,3,–g]isoquinoline), (−)-TAN-67 and (+)-TAN-67, given intracerebroventricularly (i.c.v.) on the antinociceptive response were studied in streptozotocin-induced diabetic mice using the tail-flick test. (−)-TAN-67 at doses of 3–10 μg given i.c.v. produced dose-dependent inhibition of the tail-flick response in both non-diabetic and diabetic mice. The antinociceptive effect of (−)-TAN-67 in the tail-flick test in diabetic mice was greater than that in non-diabetic mice. The antinociceptive effect of (−)-TAN-67 was not antagonized by pretreatment with either β-funaltrexamine, a selective μ-opioid receptor antagonist, or nor-binaltorphimine, a selective κ-opioid receptor antagonist. When 7-benzylidenenaltrexone, a selective δ₁-opioid receptor antagonist, was administered 10 min before treatment with (−)-TAN-67, the antinociceptive effect of (−)-TAN-67 was significantly antagonized. However, naltriben, a selective δ₂-opioid receptor antagonist, had no significant effect on the antinociceptive effect of (−)-TAN-67. On the other hand, in the tail-flick test, (+)-TAN-67 at doses of 3–30 μg given i.c.v. did not produce dose-dependent inhibition of the tail-flick response in either non-diabetic or diabetic mice. In conclusion, (−)-TAN-67, but not its enantiomer (+)-TAN-67, produced an antinociceptive effect through the activation of δ₁-opioid receptors. © 1997 Elsevier Science B.V. All rights reserved.
5-HT<inf>1D</inf> receptors
1997, Pharmacochemistry Library
The heterogeneity of receptors mediating 5-HT responses was apparent long before their definitive identification using cloning techniques, largely due to radioligand binding studies. Hence, as early as 1979, 5-HT recognition sites were subdivided into two classes. Those that had a high affinity for agonists and were labeled with [3H]5-HT were termed “5-HT₁ binding sites” and those that displayed a high affinity for antagonists and were labeled with [aH]spiperone were called “5-HT₂ binding sites.” In 1981, Pedigo demonstrated that spiperone displaced [aH]5-HT in a complex manner; hence, the 5-HT₁ class comprised at least two subgroups. The component having a high affinity for spiperone was called a “5-HT_1A recognition site” (labeled with [∼H]8-OH-DPAT) and the remaining component the “5-HT_1B binding site” (subsequently labeled with [125I]ICYP (iodocyanopindolol) in the presence of isoprenaline).
Autoradiographic localization of 5-CT-insensitive 5-HT<inf>1</inf>-like recognition sites in guinea pig and rat brain
1996, Neuropharmacology
Quantitative autoradiographic studies, with [³H]5-HT, were used to investigate the distribution of 5-CT-insensitive 5-HT₁-like (5-HT_1E/1F) recognition sites in rat and guinea pig brain. For comparison and control purposes the distribution of the closely related 5-HT_1D binding site, which is abundant in the guinea pig but not the rat, was also investigated, as well as total specific [³H]5-HT binding. Results from this study confirm the previously described regional distribution of the 5-HT_1D binding site and also revealed a predominance of 5-CT-insensitive 5-HT₁-like (5-HT_1E/1F) recognition sites in the olfactory tubercle, caudate putamen, nucleus accumbens and substantia nigra of both species. Interestingly 5-CT-insensitive 5-HT₁-like (5-HT_1E/1F) recognition sites were particularly dense in the claustrum of the guinea pig, but not the rat.
Autoradiographic analysis of 5-HT receptor subtypes labeled by [3H]5-CT ([3H]5-carboxamidotryptamine)
1995, Behavioural Brain Research
This work examines the autoradiographic distribution of serotonin (5-HT) receptor subtypes in rat, guinea pig and human brain, using [³H]5-HT and [³H]5-CT as ligands. Different displacers were used to mask radioligand binding to 5-HT_1A, $5- HT_{2B1D}$ and 5-HT_2C receptors, in an attempt to visualize other receptor populations, which presumably would correspond to 5-HT_1E and 5-HT_1F sites. Brain areas enriched in 5-HT_non1A/1B/1D sites in guinea pig were the hilus, dentate gyrus, striatum, claustrum, substantia nigra and superior colliculus, among others. In humans, however, the claustrum, a structure supposed to contain 5-HT_1E sites, showed significant densities of [³H]5-CT binding. An interesting finding was that blockade [³H]5-CT binding to 5-HT_1A receptors by 8-OH-DPAT could only be achieved at very high concentrations of the displacer. This could be due to differences in the affinity of ligands in intact tissue sections compared to membrane homogenates or cell lines. Another possibility would be that [³H]5-CT labels 5-HT_1A receptors in the low-affinity state. These hypotheses remain to be investigated.
Localization of 5-HT<inf>1B</inf>, 5-HT<inf>1Dα</inf>, 5-HT<inf>1E</inf> and 5-HT<inf>1F</inf> receptor messenger RNA in rodent and primate brain
1994, Neuropharmacology
In situ hybridization histochemistry (ISHH) was used to study the distribution of various 5-HT₁ receptor messenger RNAs (mRNA) in the mammalian nervous system. Since the cDNAs encoding the different 5-HT₁ receptors, have not been cloned in one single species, brains of the species appropriate for the 5-HT₁ receptor messenger RNA (mRNA) have been used. Thus, 5-HT_1B and 5-HT_1Dα, mRNA were determined in rat and mouse brain, while 5-HT_1E and 5-HT_1F mRNA were studied in human (and monkey) and guinea-pig brain, respectively.
5-HT_1B and 5-HT_1Dα hybridization signals were predominantly present in caudate-putamen and cortical areas; in addition, 5-HT_1B mRNA was also detected in hippocampus, cerebellum and cerebral arteries. In general, the distribution of 5-HT_1B mRNA was characterized by high densities, whereas 5-HT_1Dα mRNA was expressed at very low levels. Comparison of the localization of the mRNAs to the regional distributions of the 5-HT_1B and 5-HT_1D binding sites in rat brain (described in a previous study), revealed that both receptor subtypes could be putative presynaptic heteroreceptors, modulating the release of various neurotransmitters in the central nervous system.
The mRNA encoding the recently cloned 5-HT_1E receptor, which has low affinity for the 5-HT₁ receptor ligand 5-carboxamidotryptamine (5-CT), was localized in human brain. It was found to be present in cortical areas, caudate, putamen and amygdala, areas known to contain 5-CT insensitive 5-HT₁ binding sites.
The regional distribution of the 5-HT_1Fip mRNA was determined in guinea-pig brain: high densities were observed in various cortical areas, the hippocampal formation and claustrum, which are regions known to contain 5-CT insensitive 5-HT₁ or non 5-HT_1A/1B/1C/1D[³H]5-HT binding sites.
Altogether, this ISHH study describes the distribution of mRNAs of recently cloned 5-HT₁ receptors in rodent and primate brain and compares these results to the distribution of the heterogeneous population of 5-HT₁ binding sites.

View all citing articles on Scopus

View full text

Article preview

European Journal of Pharmacology

Abstract

References (27)

An investigation of the 5-HT_1D receptor binding affinity of 5-HT, 5-CT and sumatriptan in the CNS of seven species

Eur. J. Pharmacol.

Brain 5-HT₂ receptor binding sites in depressed suicide victims

Brain Res.

Modulation of 5-HT release by presynaptic inhibitory and facilitatory 5-HT receptor in brain slices

Adv. Biosci.

Serotonin receptors in human brain. I. Characterization and autoradiographic localization of 5-HTIp recognition sites. Apparent absence of 5-HT_1B recognition sites

Brain Res.

Serotonin receptors in human brain. II. Characterization and autoradiographic localization of 5-HT_1D and 5-HT₂ recognition sites

Brain Res.

Protein measurement with the Folin phenol reagent

J. Biol. Chem.

[³H]5-Carboxamidotryptamine labels multiple high affinity 5-HTID-like sites in guinea pig brain

Eur. J. Pharmacol.

A pharmacological analysis of the 5-HT receptor mediating inhibition of 5-HT release in the guinea pig frontal cortex

Eur. J. Pharmacol.

Quantitative autoradiography of 5-CT-sensitive 5-HT_1D and 5-CT-insensitive (5-HTIE) serotonin receptors in human brain

Neurosci. Lett.

Visualization of a novel serotonin recognition site (5-HTID) in the human brain by autoradiography

Neurosci. Lett.

Validation and analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes

Mol. Pharmacol.

5-HTID binding sites: possible subpopulations and species differences

Pharmacological characterisation of the serotonin (5-HT) autoreceptor modulating the electrically-evoked release of 3H 5-HT from slices of human frontal cortex membranes

Soc. Neurosci. Abstr.

Cited by (29)

Distribution of 5-HT receptors in the central nervous system: an update

Binding profile of the novel 5-HT(1B/1D) receptor antagonist,[<sup>3</sup>H]GR 125,743, in guinea-pig brain: a comparison with [<sup>3</sup>H]5-carboxamidotryptamine

5-HT<inf>1D</inf> receptors

Autoradiographic localization of 5-CT-insensitive 5-HT<inf>1</inf>-like recognition sites in guinea pig and rat brain

Autoradiographic analysis of 5-HT receptor subtypes labeled by [<sup>3</sup>H]5-CT ([<sup>3</sup>H]5-carboxamidotryptamine)

Localization of 5-HT<inf>1B</inf>, 5-HT<inf>1Dα</inf>, 5-HT<inf>1E</inf> and 5-HT<inf>1F</inf> receptor messenger RNA in rodent and primate brain

Regular paperThe distribution of 5-HT1D and 5-HT1E binding sites in human brain

Abstract

Eur. J. Pharmacol.

Brain Res.

Adv. Biosci.

Brain Res.

Brain Res.

J. Biol. Chem.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Neurosci. Lett.

Neurosci. Lett.

Validation and analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes

Mol. Pharmacol.

5-HTID binding sites: possible subpopulations and species differences

Pharmacological characterisation of the serotonin (5-HT) autoreceptor modulating the electrically-evoked release of 3H 5-HT from slices of human frontal cortex membranes

Soc. Neurosci. Abstr.

Regular paper
The distribution of 5-HT_1D and 5-HT_1E binding sites in human brain