[3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2B (5-HT2B) receptor

@article{Wainscott19973HRauwolscineAA,
  title={[3H]Rauwolscine: an antagonist radioligand for the cloned human 5-hydroxytryptamine2B (5-HT2B) receptor},
  author={D Bradley Wainscott and David A. Sasso and Jonathan D Kursar and Melvyn Baez and Virginia L. Lucaites and David L. G. Nelson},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={1997},
  volume={357},
  pages={17-24}
}
Abstract In previous reports, [3H]5-HT has been used to characterize the pharmacology of the rat and human 5-HT2B receptors. 5-HT, the native agonist for the 5-HT2B receptor, has a limitation in its usefulness as a radioligand since it is difficult to study the agonist low-affinity state of a G protein-coupled receptor using an agonist radioligand. When using [3H]5-HT as a radioligand, rauwolscine was determined to have relatively high affinity for the human receptor (Ki human = 14.3 ± 1.2 nM… 
Pharmacological characterisation of the agonist radioligand binding site of 5-HT2A, 5-HT2B and 5-HT2C receptors
TLDR
The results indicate the importance of defining the selectivity of pharmacological tools, which may have been over-estimated in the past, and highlights the need to find more selective agonists to investigate 5-HT2 receptor pharmacology.
5-Hydroxytryptamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
TLDR
Unique amongst the GPCRs, RNA editing produces 5-HT2C receptor isoforms that differ in function, such as efficiency and specificity of coupling to Gq/11 and also pharmacology [40, 482].
Pharmacologic Characterization of the Cloned Human Trace Amine-Associated Receptor1 (TAAR1) and Evidence for Species Differences with the Rat TAAR1
TLDR
The TAAR1 receptor exhibits a pharmacologic profile uniquely different from those of classic monoaminergic receptors, consistent with the structural information that places them in a distinct family of receptors, and suggests the potential for development of TAAR-selective agonists and antagonists to study their physiologic roles.
5-HT-2B Receptor
Synthesis, radiofluorination, and preliminary evaluation of the potential 5-HT2A receptor agonists [18 F]Cimbi-92 and [18 F]Cimbi-150.
TLDR
A 2-step, 1-pot labelling methodology of 2 tracer candidates, synthesised from easily accessible labelling precursors, and radiolabelled in acceptable radiochemical yields, sufficient for in vivo studies in domestic pigs are reported.
Evidence for 5-HT2B and 5-HT7 receptor-mediated relaxation in pulmonary arteries of weaned pigs
TLDR
The present in vitro bioassay can be used to characterize new drugs with potential agonist or antagonist properties at functional 5-HT7 receptors, and the estimated pKB values argue in favor of an involvement of 5- HT7 receptors in the direct vasorelaxant action of5-HT in the pulmonary arteries of weaned pigs.
Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid molecules with unexpected muscarinic antagonist activity.
TLDR
The fact that the naphthofurans lack LSD-like activity suggests that they do not bind to the serotonin receptor in a way such that the tricyclic naphTHofuran nucleus is bioisosteric with, and directly superimposable upon, the A, B, and C rings of LSD.
...
...

References

SHOWING 1-10 OF 27 REFERENCES
Pharmacological characteristics of the newly cloned rat 5-hydroxytryptamine2F receptor.
TLDR
The affinity of a compound for the 5-HT2F receptor at 37 degrees versus 0 degree was shown to be useful for predicting agonist or antagonist activity, and information is provided about some of the structural requirements for the affinity of certain tryptamines at the 4-HT/1C receptor family.
Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences.
TLDR
The cloned human 5-HT2B receptor has high affinity for [3H]5-HT (Kd = 10.6 +/- 1.5 nM), and the pharmacological findings reinforce the desirability of having the human forms of receptors when considering drug actions.
3H-DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) labels a guanyl nucleotide-sensitive state of cortical 5-HT2 receptors.
TLDR
3H-DOB labels a subset of brain 5-HT2 receptors that has high affinity for agonists as well as antagonists); 3H-ketanserin appears to label both subsets ofbrain 5- HT2 receptors.
4-[125I]iodo-(2,5-dimethoxy)phenylisopropylamine and [3H]ketanserin labeling of 5-hydroxytryptamine2 (5HT2) receptors in mammalian cells transfected with a rat 5HT2 cDNA: evidence for multiple states and not multiple 5HT2 receptor subtypes.
TLDR
The transfected rat 5HT2 receptor gene product contains both the guanyl nucleotide-sensitive [125I]DOI binding site and the [3H]ketanserin binding site, indicating a coupling to a GTP-binding protein, which strongly support the two-state hypothesis for the 5 HT2 receptor and do not support the multiple 5HT1 receptor subtype hypothesis.
Molecular pharmacological differences in the interaction of serotonin with 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors.
TLDR
Observations indicate that guanine nucleotide-binding protein (G protein)-coupled receptors can exhibit high affinity for neurotransmitters in both the free receptor and the G protein- coupled states and that receptors exhibiting this property may represent a novel subfamily of G protein.
High affinity agonist binding to cloned 5-hydroxytryptamine2 receptors is not sensitive to GTP analogs.
TLDR
The GTP-insensitive agonist binding is best explained by the existence of a G protein-receptor complex in 293 cells that is not sensitive to GTP analogs.
Characterization of 5-hydroxytryptamine receptors in rat stomach fundus.
TLDR
1-Arylpiperazines caused a serotonin (5-HT) receptor-mediated contraction of rat fundic strips, which resembles the 5-HT1 recognition site in rat brain cortex, but identity remains unproven.
...
...