Cited by 123Receptor Mechanisms and SignalingNeuroendocrine regulation and behaviorChemical Synthesis and Analysis

Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges

Chini, B., Manning, M.·2007·Biochemical Society Transactions

Abstract

The design and development of selective agonists acting at the OT (oxytocin)/AVP (vasopressin) receptors has been and continues to be a difficult task because of the great similarity among the different receptor subtypes as well as the high degree of chemical similarity between the active ligands. In recent decades, at least a thousand synthetic peptides have been synthesized and examined for their ability to bind to and activate the different OT/AVP receptors; an effort that has led to the identification of several receptor subtype-selective agonists in the rat. However, owing to species differences between rat and human AVP/OT receptors, these peptides do not exhibit the same selectivities in human receptor assays. Furthermore, the discovery of receptor promiscuity, which is the ability of a single receptor subtype to couple to several different G-proteins, has led to the definition of a completely new class of compounds, referred to here as coupling-selective ligands, which may activate, within a single receptor subtype, only a specific signalling pathway. Finally, the accumulating evidence that GPCRs (G-protein-coupled receptors) do not function as monomers, but as dimers/oligomers, opens up the design of another class of specific ligands, bivalent ligands, in which two agonist and/or antagonist moieties are joined by a spacer of the appropriate length to allow the simultaneous binding at the two subunits within the dimer. The pharmacological properties and selectivity profiles of these bivalent ligands, which remain to be investigated, could lead to highly novel research tools and potential therapeutic agents.

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Crossref · 10.1042/bst0350737

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Authors
Chini, B., & Manning, M.
Affiliations
  • University of Milan (IT)
  • University of Toledo (US)
Corresponding author
Chini, B.
Venue
Biochemical Society Transactions
Published
2007-07-20
Volume
35
Issue
4
Pages
737-741
ISSN
  • 0300-5127 (ISSN-L)
  • 1470-8752
OpenAlex
W2029723664
Cited by
123
References
56
Citations by year
2026: 3 · 2025: 4 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 11 · 2014: 6 · 2013: 7 · 2012: 11
FWCI
0.41
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical Society Transactions (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (GM25280, R01GM025280)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Keywords
oxytocin receptor, vasopressin receptor, receptor subtype selectivity, G protein coupling, bivalent ligands, receptor oligomerization
MeSH terms
Animals, Multigene Family, Humans, Receptors, Vasopressin, Receptors, Oxytocin

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