PMID- 10493934
OWN - NLM
STAT- MEDLINE
DCOM- 19991207
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 343 Pt 1
DP  - 1999 Oct 1
TI  - Truncated isoforms inhibit [3H]prazosin binding and cellular trafficking of
      native human alpha1A-adrenoceptors.
PG  - 231-9
AB  - We have identified from human liver eight alpha(1A)-adrenoceptor (alpha(1A)-AR)
      splice variants that were also expressed in human heart, prostate and
      hippocampus. Three of these alpha(1A)-AR isoforms (alpha(1A-1)-AR,
      alpha(1A-2a)-AR and alpha(1A-3a)-AR) gave rise to receptors with seven
      transmembrane domains (7TMalpha(1A)-AR). The other five (alpha(1A-2b)-AR,
      alpha(1A-2c)-AR, alpha(1A-3c)-AR, alpha(1A-5)-AR and alpha(1A-6)-AR) led to
      truncated receptors lacking transmembrane domain VII (6TMalpha(1A)-AR). The
      7TMalpha(1A)-AR isoforms transiently expressed in COS-7 cells bound
      [(3)H]prazosin with high affinity (K(d) 0.2 nM) and mediated a noradrenaline
      (norepinephrine)-induced increase in cytoplasmic free Ca(2+) concentration,
      whereas the 6TMalpha(1A)-AR isoforms were incapable of ligand binding and signal 
      transduction. Immunocytochemical studies with N-terminal epitope-tagged
      alpha(1A)-AR isoforms showed that the 7TMalpha(1A)-AR isoforms were present both 
      at the cell surface and in intracellular compartments, whereas the
      6TMalpha(1A)-AR isoforms were exclusively localized within the cell.
      Interestingly, in co-transfected cells, each truncated alpha(1A)-AR isoform
      inhibited [(3)H]prazosin binding and cell-surface trafficking of the co-expressed
      'original' 7TMalpha(1A-1)-AR. However, there was no modification of either the
      [(3)H]prazosin-binding affinity or the pharmacological properties of
      alpha(1A-1)-AR. Immunoblotting experiments revealed that co-expression of the
      alpha(1A-1)-AR with 6TMalpha(1A)-AR isoforms did not impair alpha(1A-1)-AR
      expression. Therefore the expression in human tissues of many truncated isoforms 
      constitutes a new regulation pathway of biological properties of alpha(1A)-AR.
FAU - Coge, F
AU  - Coge F
AD  - Institut de Recherches Servier, Division de Pharmacologie Moleculaire et
      Cellulaire, 125 chemin de Ronde, 78 290 Croissy sur Seine, France.
      coge@servier.fr
FAU - Guenin, S P
AU  - Guenin SP
FAU - Renouard-Try, A
AU  - Renouard-Try A
FAU - Rique, H
AU  - Rique H
FAU - Ouvry, C
AU  - Ouvry C
FAU - Fabry, N
AU  - Fabry N
FAU - Beauverger, P
AU  - Beauverger P
FAU - Nicolas, J P
AU  - Nicolas JP
FAU - Galizzi, J P
AU  - Galizzi JP
FAU - Boutin, J A
AU  - Boutin JA
FAU - Canet, E
AU  - Canet E
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (ADRA1A protein, human)
RN  - 0 (DNA, Complementary)
RN  - 0 (Protein Isoforms)
RN  - 0 (Receptors, Adrenergic, alpha-1)
RN  - 10028-17-8 (Tritium)
RN  - XM03YJ541D (Prazosin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Biological Transport
MH  - Blotting, Western
MH  - COS Cells
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Humans
MH  - Liver/metabolism
MH  - Molecular Sequence Data
MH  - Prazosin/*antagonists & inhibitors/metabolism
MH  - Protein Binding
MH  - Protein Isoforms/chemistry/genetics/*metabolism
MH  - Radioligand Assay
MH  - Receptors, Adrenergic, alpha-1/chemistry/genetics/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Subcellular Fractions/metabolism
MH  - Tritium
PMC - PMC1220546
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
PST - ppublish
SO  - Biochem J. 1999 Oct 1;343 Pt 1:231-9.