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PMID: 1608964 Published · ppublish English Comparative Study Journal Article

Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1-like subtype.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 12 ·1992-06-15 ·Pages 5517-21

McAllister G, Charlesworth A, Snodin C, Beer MS, Noble AJ, Middlemiss DN, Iversen LL, Whiting P

Abstract

Degenerate primers, suitable for polymerase chain reaction studies and based on the conserved structure of G protein-coupled receptors, were used to isolate cDNA clones encoding putative G protein-coupled receptors from a human hippocampal cDNA library. One clone isolated by this approach (AC1) encoded a putative receptor with 39% amino acid sequence identity to the serotonin 5HT1A receptor and 47% identity to the 5HT1D receptor. When expressed transiently in the human embryonic kidney cell line 293, AC1 cDNA-encoded receptor displayed high affinity (Kd = 15 nM) and saturability for [3H]serotonin, suggesting that AC1 encodes a 5HT1-like receptor. However, 5-carboxamidotryptamine demonstrated low affinity (pKi = 5.15) compared with serotonin (pKi = 8.14), consistent with the observed binding of the putative 5HT1E receptor. The excellent correlation observed between the pharmacology of the expressed receptor encoded by AC1 and the human brain 5HT1E binding site confirms that AC1 encodes a 5HT1E receptor and establishes a fifth 5HT1-like receptor subtype.

Related Genes
5HT1 5HT1D 5HT1E AC1
MeSH Terms
Adenylyl Cyclases/metabolism Amino Acid Sequence Base Sequence Binding, Competitive Cell Line Cloning, Molecular/methods Colforsin/pharmacology DNA/genetics,metabolism Frontal Lobe/metabolism GTP-Binding Proteins/metabolism Gene Library Hippocampus/physiology Humans Kinetics Molecular Sequence Data Oligodeoxyribonucleotides Polymerase Chain Reaction/methods Receptors, Serotonin/genetics,metabolism Recombinant Proteins/metabolism Restriction Mapping Sequence Homology, Nucleic Acid Serotonin/metabolism Transfection
Chemicals
Oligodeoxyribonucleotides Receptors, Serotonin Recombinant Proteins Colforsin Serotonin DNA GTP-Binding Proteins Adenylyl Cyclases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
McAllister G
Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.
Charlesworth A
Snodin C
Beer M S
Noble A J
Middlemiss D N
Iversen L L
Whiting P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.12.5517
Published
1992-06-15
Pages
5517-21
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC49323
Subset
IM
Databases
GENBANK
M91467
External Links
PubMed source DOI: 10.1073/pnas.89.12.5517 PMC Full Text View journal details
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