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Molecular Pharmacology

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Rapid CommunicationAccelerated Communication

Molecular Cloning and Pharmacological Characterization of a New Galanin Receptor Subtype

Suke Wang, Tanaz Hashemi, Chaogang He, Catherine Strader and Marvin Bayne
Molecular Pharmacology September 1997, 52 (3) 337-343; DOI: https://doi.org/10.1124/mol.52.3.337
Suke Wang
The Schering-Plough Research Institute, Kenilworth, New Jersey 07033
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Tanaz Hashemi
The Schering-Plough Research Institute, Kenilworth, New Jersey 07033
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Chaogang He
The Schering-Plough Research Institute, Kenilworth, New Jersey 07033
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Catherine Strader
The Schering-Plough Research Institute, Kenilworth, New Jersey 07033
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Marvin Bayne
The Schering-Plough Research Institute, Kenilworth, New Jersey 07033
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Abstract

Galanin, a 29–30-amino acid neuropeptide, is widely distributed in central and peripheral systems and mediates a variety of physiological functions. Pharmacological studies have suggested the existence of multiple receptor subtypes but only the type I (GalR1) galanin receptor has been cloned. Now we report the cloning by a combination of sib selection and rapid amplification of cDNA ends of a cDNA encoding a new galanin receptor (GalR2) from rat hypothalamus. The receptor is 372 amino acids in length and shares only 40% homology with the rat GalR1 receptor. It contains seven putative transmembrane domains with the amino and carboxyl termini being least identical to GalR1. Northern blot analyses revealed a 2-kilobase pair mRNA species distributed in several tissues, suggesting a broader functional spectrum than GalR1.125I-Labeled human galanin binding to rat GalR2 receptor expressed in COS-1 cells was saturable (Kd = 0.59 nm) and could be displaced by galanin, several galanin fragments, and chimeric peptides. The pharmacological profiles of GalR1 and GalR2 receptors were distinguishable by galanin fragment(2–29), which bound the cloned GalR2 receptor with markedly higher affinity than the GalR1 receptor. Activation of the cloned receptor by galanin led to inhibition of forskolin-stimulated intracellular cAMP production. The cloning of this new receptor subtype should provide further insights into the mechanisms by which galanin mediates its diverse physiological functions. The identification of galanin(2–29) as a receptor-specific ligand should enhance the understanding of specificity of galanin-receptor interactions.

Footnotes

    • Received April 10, 1997.
    • Accepted May 19, 1997.
  • Send reprint requests to: Dr. Suke Wang, Schering-Plough Research Institute, 2015 Galloping Hill Road, K15-C331–3600, Kenilworth, NJ 07033. E-mail:suke.wang{at}spcorp.com

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 52 (3)
Molecular Pharmacology
Vol. 52, Issue 3
1 Sep 1997
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Rapid CommunicationAccelerated Communication

Molecular Cloning and Pharmacological Characterization of a New Galanin Receptor Subtype

Suke Wang, Tanaz Hashemi, Chaogang He, Catherine Strader and Marvin Bayne
Molecular Pharmacology September 1, 1997, 52 (3) 337-343; DOI: https://doi.org/10.1124/mol.52.3.337

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Rapid CommunicationAccelerated Communication

Molecular Cloning and Pharmacological Characterization of a New Galanin Receptor Subtype

Suke Wang, Tanaz Hashemi, Chaogang He, Catherine Strader and Marvin Bayne
Molecular Pharmacology September 1, 1997, 52 (3) 337-343; DOI: https://doi.org/10.1124/mol.52.3.337
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