PMID- 23029047
OWN - NLM
STAT- MEDLINE
DCOM- 20130306
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 9
DP  - 2012
TI  - The cardiac ventricular 5-HT4 receptor is functional in late foetal development 
      and is reactivated in heart failure.
PG  - e45489
LID - 10.1371/journal.pone.0045489 [doi]
LID - e45489
AB  - A positive inotropic responsiveness to serotonin, mediated by 5-HT(4) and 
      5-HT(2A) receptors, appears in the ventricle of rats with post-infarction 
      congestive heart failure (HF) and pressure overload-induced hypertrophy. A 
      hallmark of HF is a transition towards a foetal genotype which correlates with 
      loss of cardiac functions. Thus, we wanted to investigate whether the foetal and 
      neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts 
      were collected day 3 and 1 before expected birth (days -3 and -1), as well as day 
      1, 3, 5 and 113 (age matched with Sham and HF) after birth. Hearts from 
      post-infarction HF and sham-operated animals (Sham) were also collected. Heart 
      tissue was examined for mRNA expression of 5-HT(4), 5-HT(2A) and 5-HT(2B) 
      serotonin receptors, 5-HT transporter, atrial natriuretic peptide (ANP) and 
      myosin heavy chain (MHC)-alpha and MHC-beta (real-time quantitative RT-PCR) as well as 
      5-HT-receptor-mediated increase in contractile function exvivo (electrical field 
      stimulation of ventricular strips from foetal and neonatal rats and left 
      ventricular papillary muscle from adult rats in organ bath). Both 5-HT(4) mRNA 
      expression and functional responses were highest at day -3 and decreased 
      gradually to day 5, with a further decrease to adult levels. In HF, receptor mRNA 
      levels and functional responses reappeared, but to lower levels than in the 
      foetal ventricle. The 5-HT(2A) and 5-HT(2B) receptor mRNA levels increased to a 
      maximum immediately after birth, but of these, only the 5-HT(2A) receptor 
      mediated a positive inotropic response. We suggest that the 5-HT(4) receptor is a 
      representative of a foetal cardiac gene program, functional in late foetal 
      development and reactivated in heart failure.
FAU - Brattelid, Trond
AU  - Brattelid T
AD  - Department of Pharmacology, Faculty of Medicine, University of Oslo and Oslo 
      University Hospital, Oslo, Norway.
FAU - Qvigstad, Eirik
AU  - Qvigstad E
FAU - Moltzau, Lise R
AU  - Moltzau LR
FAU - Bekkevold, Silje V S
AU  - Bekkevold SV
FAU - Sandnes, Dagny L
AU  - Sandnes DL
FAU - Birkeland, Jon Arne K
AU  - Birkeland JA
FAU - Skomedal, Tor
AU  - Skomedal T
FAU - Osnes, Jan-Bjorn
AU  - Osnes JB
FAU - Sjaastad, Ivar
AU  - Sjaastad I
FAU - Levy, Finn Olav
AU  - Levy FO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120920
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 158165-40-3 (Receptors, Serotonin, 5-HT4)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetal Development/*genetics
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Developmental
MH  - Heart Failure/*genetics/metabolism
MH  - Heart Ventricles/*metabolism
MH  - Male
MH  - Myocardial Contraction/genetics
MH  - Phenotype
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Receptors, Adrenergic, beta/genetics/metabolism
MH  - Receptors, Serotonin, 5-HT4/*genetics/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
PMC - PMC3447799
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/10/03 06:00
MHDA- 2013/03/07 06:00
PMCR- 2012/09/20
CRDT- 2012/10/03 06:00
PHST- 2011/04/15 00:00 [received]
PHST- 2012/08/23 00:00 [accepted]
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/03/07 06:00 [medline]
PHST- 2012/09/20 00:00 [pmc-release]
AID - PONE-D-11-06937 [pii]
AID - 10.1371/journal.pone.0045489 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(9):e45489. doi: 10.1371/journal.pone.0045489. Epub 2012 Sep 20.