Molecular Cloning of a Functional Human Galanin Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-10, Vol.91 (21), p.9780-9783
• Main Authors: Habert-Ortoli, Estelle, Amiranoff, Brigitte, Loquet, Isabelle, Laburthe, Marc, Mayaux, Jean-François
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino acids; Anatomy & physiology; Animals; Cell Cycle; Cell Line; Cell lines; Cell Membrane - metabolism; Cell membranes; Cercopithecus aethiops; Cloning, Molecular; Complementary DNA; COS cells; Deoxyribonucleic acid; DNA; Galanin; Galanin receptors; HT29 cells; Humans; Kidney; Kinetics; Molecular Sequence Data; Neuropeptides - metabolism; Peptides - metabolism; Proteins; Receptors; Receptors, Galanin; Receptors, Gastrointestinal Hormone - biosynthesis; Receptors, Gastrointestinal Hormone - metabolism; Recombinant Proteins - metabolism; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; RNA, Messenger - metabolism; Sequence Homology, Amino Acid; Signal Transduction; Transfection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.21.9780

The ubiquitous neuropeptide galanin controls numerous functions such as endocrine secretions, intestinal motility, and behavioral activities. These regulatory effects of galanin are mediated through the interaction with specific membrane receptors and involve the pertussis toxin-sensitive guanine nucleotide binding proteins Gi/Goas transducing elements. We report here the isolation of a cDNA coding for a human galanin receptor from a Bowes melanoma cell line cDNA expression library, by using a radioligand binding strategy. The nucleotide sequence of the cloned receptor reveals an open reading frame encoding a 349-amino acid protein with seven putative hydrophobic transmembrane domains and significant homology with members of the guanine nucleotide binding protein-coupled neuropeptide receptor family. The cloned receptor expressed in COS cells specifically binds human, porcine, and rat galanin with high affinity (Kdin the nanomolar range) and mediates the galanin inhibition of adenylate cyclase. A 2.8-kb galanin receptor transcript was identified in several human tissues. Cloning of this galanin receptor should enhance our knowledge of its distribution, structure, and function in human physiology and pathophysiology.