Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes

@article{Peroutka1989IdentificationO5,
  title={Identification of 5‐hydroxytryptamine1D binding sites in human brain membranes},
  author={Stephen J. Peroutka and Jeffrey A. Switzer and Anne Hamik},
  journal={Synapse},
  year={1989},
  volume={3}
}
High‐affinity, specific 3H‐5‐hydroxytryptamine (5‐HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5‐HT1A and 5‐HT1C binding sites were pharmacologically blocked using 100 nM 8‐hydroxy‐N,N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT) and 100 nM mesulergine, respectively. The majority of 5‐HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP… 
Binding studies with the 5‐HT1B receptor agonist [3H]CP‐96,501 in brain tissues
TLDR
Negligible specific binding of [3H]CP‐96,501 was found in membranes of guinea pig brain, dog hypothalamus, bovine caudate, pig choroid plexus, and several human brain tissues, consistent with the reported absence of the 5‐HT1B receptor subtype in these species.
Identification of 5-hydroxytryptamine1D binding sites in sheep caudate nucleus membranes.
TLDR
The present results indicate that sheep caudate nucleus is a valid tissue for studying interaction of compounds with 5- HT1D binding sites in the relative absence of 5-HT1E binding sites.
[3H]5-hydroxytryptamine binding sites in postmortem human brain
TLDR
Self-displacement of the binding of [3H]5-HT is consistent with the presence of a single population of sites, indicating that 5- HT is non-selective for the 5-HT1 subtypes.
L‐694,247: a potent 5‐HT1D receptor agonist
TLDR
The excellent agreement observed for L‐694,247 between the 5‐HT1D radioligand binding affinity and the functional potency confirm that the two functional models (the inhibition of forskolin‐stimulated adenylyl cyclase in guinea‐pig substantia nigra and the inhibition of K+‐evoked [3H]‐5‐HT release from guinea-pig frontal cortex) do indeed reflect 5‐ HT1D‐mediated events.
Cortical and striatal variations in drug competition studies with putative 5-hydroxytryptamine1D binding sites
TLDR
The ability of 5-hydroxytryptamine, 5-carboxytryptamine and sumatriptan to compete for [3H]5-HT binding sites in various brain tissues was analyzed and it is indicated that 10(-5) M 5-HT should not be used to define specific binding to 5- HT1D receptors in radioligand binding assays.
Preservation of 5-hydroxytryptamine1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's disease
TLDR
The results suggest that the 5-HT1A receptor-G protein complex is functionally intact in these regions in Alzheimer's disease brain.
5-benzyloxytryptamine: a relatively selective 5-hydroxytryptamine 1D/1B agent.
TLDR
5-BT is a relatively selective partial agonist at 5-HT1D receptors, and additional radioligand binding studies with 5-BT indicate that the drug shows relative selectivity for 5- HT1D/1B binding sites.
An investigation of the 5-HT1D receptor binding affinity of 5-hydroxytryptamine, 5-carboxyamidotryptamine and sumatriptan in the central nervous system of seven species.
TLDR
Data indicate that under these experimental conditions the high affinity component labelled by [3H]5-HT is the same receptor subtype, previously denoted the 5-HT1D receptor, in all seven species.
Structural determinants of 5-HT1A versus 5-HT1D receptor binding site selectivity.
TLDR
7 agents identified are the most selective agents yet described for 5- HT1A versus 5-HT1D receptor binding sites and 4 of the agents are greater than 100-fold selective.
Altered G-protein coupling of a frontal cortical low affinity [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin serotonergic binding site in Alzheimer's disease
TLDR
Findings suggest that alterations in receptor/G-protein coupling of both cholinergic and serotonergic receptors may be one explanation why neurotransmitter replacement drug therapies have been unsuccessful thus far in the treatment of AD.
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TLDR
This putative novel 5‐HT receptor has a similar pharmacology to the “5‐HT1D” site detected in bovine brain by Heuring and Peroutka and is also detectable in human caudate.
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TLDR
The present data suggest the presence of three independent 5‐HT1 binding sites having different affinities for mianserin and spiperone and having different regional distributions.
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TLDR
Saturation studies of [3H]5‐HT binding assayed in the absence or presence of 1 μM‐spiperone reveal a parallel shift in the Scatchard plot with no change in the dissociation constant of [2‐12 nM], but a significant decrease in the number of specific binding sites.
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TLDR
Computer‐assisted iterative curve fitting suggests that these drugs can discriminate two distinct subpopulations of non‐5‐ HT1A binding sites, each representing ∼35% of the total [3H]5‐HT binding in the rat frontal cortex.
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TLDR
The postsynaptic hippocampal [3H]8‐OH‐DPAT binding sites are probably identical to the 5‐HT1A, subsites, but the relationship between the presynaptic binding sites and the Presynaptic autoreceptors controlling 5‐ HT release deserves further investigation.
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TLDR
The present data are consistent with the concept of multiple 5‐HT1 binding sites and suggest the presence of at least two, and perhaps as many as three, groups of sites in the mammalian brain.
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TLDR
The data demonstrate the presence of a homogeneous class of 5- HT1 binding sites in bovine caudate that is pharmacologically distinct from previously defined 5-HT1A, 5-ht1B, 5 - HT1C, 4-HT2, 3-HT3 receptor subtypes.
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TLDR
Computer-assisted iterative curve fitting of RU 24969 competition studies indicate that RU 249 69 distinguishes two distinct components of non-5-HT1A sites in rat and mouse brain.
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The effect of age on the binding of [3H]5‐hydroxytryptamine ([3H]5‐HT, serotonin) to postmortem human frontal cortex, hippocampus, and putamen from individuals between the ages of 19 and 100 years
Ca2+‐Guanine Nucleotide Interactions in Brain Membranes. I. Modulation of Central 5‐Hydroxytryptamine Receptors in the Rat
TLDR
It is indicated that central 5‐hydroxytryptamine (5‐HT; serotonin) receptors can be modulated in opposite directions by Ca2+ and guanine nucleotides and compatible with the hypothesis of a possible coupling of some–but not all–[3H]5‐ HT binding sites to adenylate cyclase in the rat brain.
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