PMID- 10646498
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 74
IP  - 2
DP  - 2000 Feb
TI  - Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4
      splice variant.
PG  - 478-89
AB  - Several variants of the serotonin 5-HT4 receptor are known to be produced by
      alternative splicing. To survey the existence and usage of exons in humans, we
      cloned the human 5-HT4 gene. Based on sequence analysis seven C-terminal variants
      (a-g) and one internal splice variant (h) were found. We concentrated in this
      study on the functional characterization of the novel splice variant h, which
      leads to the insertion of 14 amino acids into the second extracellular loop of
      the receptor. The h variant was cloned as a splice combination with the
      C-terminal b variant; therefore, we call this receptor 5-HT4(hb). This novel
      receptor variant was expressed transiently in COS-7 cells, and its
      pharmacological profile was compared with those of the previously cloned 5-HT4(a)
      and 5-HT4(b) isoforms, with the latter being the primary reference for the h
      variant. In competition binding experiments using reference 5-HT4 ligands, no
      significant differences were detected. However, the broadly used 5-HT4 antagonist
      GR113808 discriminated functionally among the receptor variants investigated. As 
      expected, it was an antagonist on the 5-HT4(a) and 5-HT4(b) variant but showed
      partial agonistic activity on the 5-HT4(hb) variant. These data emphasize the
      importance of variations introduced by splicing for receptor pharmacology and may
      help in the understanding of conflicting results seen with 5-HT4 ligands in
      different model systems.
FAU - Bender, E
AU  - Bender E
AD  - Department of Functional Genomics, Janssen Research Foundation, Beerse, Belgium. 
      ebender@janbe.jnj.com
FAU - Pindon, A
AU  - Pindon A
FAU - van Oers, I
AU  - van Oers I
FAU - Zhang, Y B
AU  - Zhang YB
FAU - Gommeren, W
AU  - Gommeren W
FAU - Verhasselt, P
AU  - Verhasselt P
FAU - Jurzak, M
AU  - Jurzak M
FAU - Leysen, J
AU  - Leysen J
FAU - Luyten, W
AU  - Luyten W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (DNA, Recombinant)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Serotonin)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Animals
MH  - Base Sequence/genetics
MH  - COS Cells
MH  - *Cloning, Molecular
MH  - *DNA, Recombinant
MH  - *Genetic Variation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Isoforms/genetics
MH  - RNA, Messenger/metabolism
MH  - Receptors, Serotonin/*genetics/metabolism
MH  - Tissue Distribution
EDAT- 2000/01/26 00:00
MHDA- 2000/01/26 00:01
CRDT- 2000/01/26 00:00
PHST- 2000/01/26 00:00 [pubmed]
PHST- 2000/01/26 00:01 [medline]
PHST- 2000/01/26 00:00 [entrez]
AID - 10.1046/j.1471-4159.2000.740478.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Feb;74(2):478-89. doi: 10.1046/j.1471-4159.2000.740478.x.