PMID- 10598591
OWN - NLM
STAT- MEDLINE
DCOM- 20000110
LR  - 20100825
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 12
DP  - 1999 Dec
TI  - A novel spliced variant of the type 1 corticotropin-releasing hormone receptor
      with a deletion in the seventh transmembrane domain present in the human pregnant
      term myometrium and fetal membranes.
PG  - 2189-202
AB  - CRH exerts its actions via activation of specific G protein-coupled receptors,
      which exist in two types, CRH-R1 and CRH-R2, and arise from different genes with 
      multiple spliced variants. RT-PCR amplification of CRH receptor sequences from
      human myometrium and fetal membranes yielded cDNAs that encode a novel CRH-R type
      1 spliced variant. This variant (CRH-R1d) is present in the human pregnant
      myometrium at term only, which suggests a physiologically important role at the
      end of human pregnancy and labor. The amino acid sequence of CRH-R1d is identical
      to the CRH-R1alpha receptor except that it contains an exon deletion resulting in
      the absence of 14 amino acids in the predicted seventh transmembrane domain.
      Binding studies in HEK-293 cells stably expressing the CRH-R1d or CRH-R1alpha
      receptors revealed that the deletion does not change the binding characteristics 
      of the variant receptor. In contrast, studies on the G protein activation
      demonstrated that CRH-R1d is not well coupled to the four subtypes of G proteins 
      (G(s), G(i), G(o), G(q)) that CRH-R1alpha can activate. These data suggest that
      although the deleted segment is not important for CRH binding, it plays a crucial
      role in CRH receptor signal transduction. Second messenger studies of the variant
      receptor showed that CRH and CRH-like peptides can stimulate the adenylate
      cyclase system, with reduced sensitivity and potency by 10-fold compared with the
      CRH-R1alpha. Furthermore, CRH failed to stimulate inositol trisphosphate
      production. Coexpression studies between the CRH-R1d or CRH-R1alpha showed that
      this receptor does not play a role as a dominant negative receptor for CRH.
FAU - Grammatopoulos, D K
AU  - Grammatopoulos DK
AD  - Sir Quinton Hazell Molecular Medicine Research Centre, Department of Biological
      Sciences, University of Warwick, Coventry, United Kingdom.
      chdg@dna.bio.warwick.ac.uk
FAU - Dai, Y
AU  - Dai Y
FAU - Randeva, H S
AU  - Randeva HS
FAU - Levine, M A
AU  - Levine MA
FAU - Karteris, E
AU  - Karteris E
FAU - Easton, A J
AU  - Easton AJ
FAU - Hillhouse, E W
AU  - Hillhouse EW
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
SB  - IM
MH  - *Alternative Splicing
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Membrane/chemistry
MH  - Corticotropin-Releasing Hormone/pharmacology
MH  - Extraembryonic Membranes/*chemistry
MH  - Female
MH  - *Gene Deletion
MH  - Humans
MH  - Immunosorbent Techniques
MH  - Kidney
MH  - Molecular Sequence Data
MH  - Myometrium/*chemistry
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Receptors, Corticotropin-Releasing Hormone/analysis/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1210/mend.13.12.0391 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Dec;13(12):2189-202. doi: 10.1210/mend.13.12.0391.