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Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- We have cloned a novel C-terminal splice variant of serotonin 5-HT4 receptors from human hippocampus. The deduced protein extends only one aminoacid past the splicing point. We propose to call the novel variant h5-HT4(n) since it contains none of the C-terminal exons alternatively spliced in other variants. The pharmacological profile of h5-HT4(n) stably expressed in HeLa cells is in agreement with other reported variants. Stably transfected cells showed increased basal levels of intracellular cAMP in absence of agonist, indicating constitutive activity of the expressed receptors. 5-HT induced robust increases of intracellular cAMP. The 5-HT4 receptor antagonist GR 113808 blocked the effects of 5-HT and brought intracellular cAMP below basal constitutive levels, indicating inverse agonism of this compound in this system. The RT-PCR distribution of all known human C-terminal splice variants in human brain regions and periphery showed complex patterns of variant expression, with the novel variant h5-HT4(n) being widely and abundantly expressed. © 2002 Elsevier Science Ltd. All rights reserved.<br />This work was supported by grants from CICYT, SAF 96-0336 and SAF 97-0117. In the very initial phases of this project, M.T.V. was recipient of a Long Term EMBO fellowship (ALTF 448-1992). Support from the CIRIT (Generalitat de Catalunya) to the Department of Neurochemistry (IIBB/CSIC) as Grup de Recerca Consolidat (1999 SGR-00210) is acknowledged
- Subjects :
- Male
Agonist
DNA, Complementary
medicine.drug_class
In Vitro Techniques
Biology
[3H]GR 113808
5-HT4 receptors
Hippocampus
Cell Line
5-HT7 receptor
Radioligand Assay
Cellular and Molecular Neuroscience
Exon
Receptor constitutive activity
Peripheral Nervous System
Cyclic AMP
medicine
Animals
Humans
splice
RNA, Messenger
Cloning, Molecular
Receptor
Brain Chemistry
Pharmacology
Genetics
Reverse Transcriptase Polymerase Chain Reaction
Cell Membrane
Alternative splicing
Exons
Oligonucleotides, Antisense
musculoskeletal system
Receptor antagonist
Molecular biology
Alternative Splicing
Macaca fascicularis
C-terminal splice variants
Receptors, Serotonin
RNA splicing
Human brain distribution
Female
Receptors, Serotonin, 5-HT4
Subjects
Details
- ISSN :
- 00283908
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Neuropharmacology
- Accession number :
- edsair.doi.dedup.....2c575f8a786f7e769c0c84c06fb2b2a8