Document Detail


Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.
MedLine Citation:
PMID:  9092793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
GH release is thought to occur under the reciprocal regulation of two hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. In addition, GH-releasing peptides, such as GHRP-6 and the nonpeptide mimetics, L-692,429 and MK-0677, stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHS-R). The recent cloning of the GHS-R from human and swine pituitary gland identifies yet a third G protein-coupled receptor (GPC-R) involved in the control of GH release and further supports the existence of an undiscovered hormone that may activate this receptor. Using the human GHS-R as a probe, we report the isolation of a rat pituitary GHS-R cDNA derived from an unspliced, precursor mRNA. The rat cDNA encodes a protein of 364 amino acids containing seven transmembrane domains (7-TM) with >90% sequence identity to both the human and swine GHS-Rs. A single intron of approximately 2 kb divides the open reading frame into two exons encoding TM 1-5 and TM 6-7, thus placing the GHS-R into the intron-containing class of GPC-Rs. The intron maps to the site of sequence divergence between the human and swine type 1a and 1b GHS-R mRNAs. In addition, determination of the nucleotide sequence for the human GHS-R gene confirmed the position of an intron in the human GHS-R gene at this position. A full-length contiguous cDNA from rat hypothalamus was isolated and shown to be identical in its nucleotide and deduced amino acid sequence to the rat pituitary GHS-R. The cloned rat GHS-R binds [35S]MK-0677 with high affinity [dissociation constant (K(D)) = 0.7 nM] and is functionally active when expressed in HEK-293 cells. Expression of the rat GHS-R was observed specifically in the pituitary and hypothalamus when compared with control tissues.
Authors:
K K McKee; O C Palyha; S D Feighner; D L Hreniuk; C P Tan; M S Phillips; R G Smith; L H Van der Ploeg; A D Howard
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  11     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-08-26     Completed Date:  1997-08-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  415-23     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/U94321
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Cell Line
Cloning, Molecular
Conserved Sequence
DNA, Complementary
Humans
Hypothalamus / metabolism*
In Situ Hybridization
Indoles / metabolism
Introns
Kinetics
Molecular Sequence Data
Open Reading Frames
Pituitary Gland / metabolism*
RNA Precursors
Rats
Receptors, Cell Surface / genetics*
Receptors, G-Protein-Coupled*
Receptors, Ghrelin
Receptors, Somatotropin / biosynthesis,  genetics*
Sequence Alignment
Spiro Compounds / metabolism
Swine
Transfection
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Indoles; 0/L 163191; 0/RNA Precursors; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Receptors, Ghrelin; 0/Receptors, Somatotropin; 0/Spiro Compounds

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