Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8547-51.

Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation.

Author information

1
Unite de Neurobiologie et Pharmacologie (U. 109), l'Institut National de la Santé et de la Recherche Médicale, Centre Paul Broca, Paris, France.

Abstract

By using a strategy based on nucleotide sequence homology, we have cloned a cDNA encoding a functional serotonin (5-HT) receptor. The deduced amino acid sequence of the 5-HT7 receptor displays limited homology with that of other 5-HT receptors. In addition to the seven stretches of hydrophobic amino acids that characterize the superfamily of receptors interacting with guanine nucleotide-binding proteins, the 448-aa sequence of the 5-HT7 receptor contains a hydrophobic domain located at its N-terminal end. Genomic analysis indicated the presence of introns interrupting the coding sequence. The 5-HT7 receptor, stably expressed in transfected CHO cells, bound [3H]5-HT with high affinity (Kd = 1 nM), like receptors of the 5-HT1 subfamily from which, however, it was clearly distinguished by its pharmacology. 5-HT in nanomolar concentrations stimulated cAMP accumulation in these CHO cells by approximately 10-fold, whereas lysergic acid diethylamide displayed low intrinsic agonist activity. These various properties differentiate the 5-HT7 receptor from the four other subfamilies of mammalian 5-HT receptors (i.e., the 5-HT1-, 5-HT2-, 5-HT3-, and 5-HT4-like subfamilies) and, therefore, appear to define another receptor subfamily. Northern blot and in situ hybridization analyses showed the 5-HT7 transcripts to be expressed in discrete areas of the limbic brain (e.g., pyramidal hippocampus cells, tenia tecta, amygdaloid, or mammillary nuclei), suggesting that the receptor mediates serotoninergic controls in functions like mood, learning, or neuroendocrine and vegetative behaviors.

PMID:
8397408
PMCID:
PMC47394
DOI:
10.1073/pnas.90.18.8547
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center