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Title: Molecular cloning, genomic organization and selective expression of bombesin receptor subtype 3 in the sheep hypothalamus and pituitary.
Austin Authors: Whitley, J C;Moore, C;Giraud, A S;Shulkes, Arthur
Affiliation: University of Melbourne Department of Surgery, Austin and Repatriation Medical Centre, Austin Campus, Melbourne, Victoria, Australia
Issue Date: 1-Aug-1999
Publication information: Journal of Molecular Endocrinology; 23(1): 107-16
Abstract: The bombesin receptor subtype 3 (BRS-3) is considered an orphan receptor as it has a low affinity for bombesin-like peptides and no identified natural ligand. We have reported a novel form of gastrin-releasing peptide (GRP) present in high abundance in the pregnant uterus of women and sheep. As BRS-3 was originally cloned from guinea pig uterus, we postulated that the uterine GRP-like peptide may be its natural ligand. We have therefore cloned the gene for the sheep homologue of BRS-3 and determined its distribution. The sheep BRS-3 gene spans 4 kbp and comprises three exons with intron-exon borders at positions similar to those observed for the human and mouse BRS-3 genes. The predicted amino acid sequence of ovine BRS-3 has approximately 85% identity with the human, mouse and guinea pig receptors. Highly conserved amino acids important in mediating receptor G-protein coupling to second messengers and important in ligand binding were found to be conserved in ovine BRS-3. One potentially important deviation was noted: ovine BRS-3 possesses an arginine residue at position 294 instead of a histidine residue as found in all other BRS-3. His(294) was previously identified as important in ligand-receptor interactions while Arg(294) was implicated in high ligand affinity. Thus ovine BRS-3 may have binding characteristics different from those of the human, mouse and guinea pig BRS-3 receptors. In the ewe, BRS-3 mRNA expression was detected in pituitary and hypothalamus but not in tissues of the pregnant uterus (endometrium, myometrium, chorioallantois or amnion). Nor was BRS-3 expression detected in the non-pregnant uterus or in testis. This pattern of BRS-3 expression is similar to that observed in the mouse but different from that observed in the human, rat and guinea pig. We conclude that there is no local interaction between uterine GRP-like peptide and BRS-3. However, the high expression of BRS-3 in the pituitary coupled with elevated circulating levels of this GRP-like peptide during pregnancy suggests an alternate pathway. Cloning of the ovine BRS-3 gene will permit a detailed functional analysis of this receptor in the sheep and its role in the mediation of action of uterine GRP.
Gov't Doc #: 10425452
Journal: Journal of molecular endocrinology
Type: Journal Article
Subjects: Amino Acid Sequence
Base Sequence
Cloning, Molecular
DNA.chemistry.genetics.isolation & purification
Gene Expression Regulation
Molecular Sequence Data
Pituitary Gland.metabolism
RNA, Messenger.genetics.metabolism
Receptors, Bombesin.genetics
Restriction Mapping
Reverse Transcriptase Polymerase Chain Reaction
Sequence Alignment
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Tissue Distribution
Appears in Collections:Journal articles

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