Separate agonist and peptide antagonist binding sites of the oxytocin receptor defined by their transfer into the V2 vasopressin receptor.

The Journal of Biological Chemistry
R PostinaF Fahrenholz

Abstract

The neurohypophyseal nonapeptide oxytocin (OT) is the main hormone responsible for the initiation of labor; uterus contraction can be enhanced by application of oxytocin or suppressed by oxytocin antagonists. By transfer of domains from the G protein-coupled OT receptor into the related V2 vasopressin receptor, chimeric "gain in function" V2/OT receptors were produced that were able to bind either OT receptor agonists or a competitive peptide antagonist with high affinity. The binding site for the OT antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr9]vasotocin was found to be formed by transmembrane helices 1, 2, and 7 with a major contribution to binding affinity by the upper part of helix 7. These transmembrane receptor regions could be excluded from participating in OT binding. For agonist binding and selectivity the first three extracellular receptor domains were most important. The interaction of the N-terminal domain and of the first extracellular loop of the OT receptor with the linear C-terminal tripeptidic part of oxytocin was demonstrated. Furthermore, the second extracellular loop of the OT receptor could be identified to interact with the cyclic hormone part. These three domains contribute to OT binding by synergistic inter...Continue Reading

References

Apr 9, 1992·Nature·T KimuraH Okayama
Jun 12, 1992·Annals of the New York Academy of Sciences·C S CarterT R Insel
Jan 1, 1992·Neuroscience and Biobehavioral Reviews·C S Carter
Dec 1, 1990·American Journal of Obstetrics and Gynecology·A R FuchsM Fields
Mar 1, 1988·European Journal of Pharmacology·J ElandsW H Sawyer
Nov 15, 1984·American Journal of Obstetrics and Gynecology·A R FuchsM S Soloff
Feb 1, 1995·Biochemical Society Transactions·J HowlM Wheatley
Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·F RozenH H Zingg
Mar 24, 1995·The Journal of Biological Chemistry·E Kojro, F Fahrenholz
Oct 1, 1994·European Journal of Endocrinology·T KimuraY Tokugawa
Apr 22, 1993·Nature·G F SchertlerR Henderson
Dec 1, 1995·DNA and Cell Biology·R BathgateR Ivell
Feb 2, 1996·The Journal of Biological Chemistry·T MizobeB K Kobilka
Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·H HausmannD Richter
Dec 10, 1995·Analytical Biochemistry·R Postina, F Fahrenholz
Oct 1, 1995·Journal of Molecular Endocrinology·P R RileyH J Stewart

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Citations

Jul 23, 2003·European Journal of Pharmacology·Masaki KawamataKatsuhiko Nishimori
Jun 27, 2003·Trends in Endocrinology and Metabolism : TEM·Hans H Zingg, Stephane A Laporte
Nov 24, 1999·European Journal of Biochemistry·E KojroF Fahrenholz
Apr 28, 2000·European Journal of Biochemistry·G Gimpl, F Fahrenholz
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·M ThibonnierM Shoham
Nov 5, 2010·PloS One·Bogdan A DanalacheMarek Jankowski
Apr 6, 2012·PloS One·Thejkiran Pitti, Narayanan Manoj
Dec 31, 2002·Journal of Receptor and Signal Transduction Research·E PolitowskaJ Ciarkowsk
Dec 1, 2007·Expert Opinion on Drug Discovery·Balázs JójártArpád Márki
Dec 20, 2011·European Journal of Pharmacology·Volker Wiegand, Gerald Gimpl
Jul 3, 2010·Pharmacology, Biochemistry, and Behavior·Pawel K OlszewskiAllen S Levine
Apr 8, 2010·Neuroscience Letters·Gerardo Rojas-PiloniCondés-Lara Miguel
Mar 20, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Emilia A LubeckaJerzy Ciarkowski
Oct 11, 2011·Developmental Cognitive Neuroscience·Ilanit GordonJames F Leckman
Jul 22, 2006·Journal of Molecular Graphics & Modelling·Balázs Jójárt, Arpád Márki
Oct 7, 2015·Frontiers in Neuroscience·Danielle A Baribeau, Evdokia Anagnostou
May 13, 2015·Molecular and Cellular Endocrinology·Araceli Gonzalez-ReyesMarek Jankowski
Mar 11, 1999·Journal of Receptor and Signal Transduction Research·C CzaplewskiJ Ciarkowski
Nov 7, 2014·Journal of Biomolecular Structure & Dynamics·Ashok Kumar Kulkarni, Rajendra Prasad Ojha
Mar 15, 2013·Molecular Phylogenetics and Evolution·Kaoru Yamashita, Takashi Kitano
Oct 15, 1998·Experimental Cell Research·R PfeifferF Fahrenholz
Oct 3, 2002·Neuropeptides·J T Winslow, T R Insel
Feb 26, 2016·Reproduction : the Official Journal of the Society for the Study of Fertility·Keisuke KozaiKiyoshi Okuda
May 6, 2015·PloS One·Dongren RenJeffrey A French
Jul 29, 2008·Progress in Brain Research·Gerald GimplConny Trossen
May 1, 2017·American Journal of Obstetrics and Gynecology·Erin L ReinlSarah K England
Sep 11, 2004·Bioorganic & Medicinal Chemistry Letters·Gary R W PittMichael B Roe
Jun 14, 2018·Physiological Reviews·Benjamin Jurek, Inga D Neumann
Aug 23, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Magdalena J SlusarzJerzy Ciarkowski
Aug 23, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Magdalena J SlusarzJerzy Ciarkowski
Mar 13, 2012·Pharmacological Reviews·Richard J LewisMacDonald J Christie
Oct 28, 2019·Journal of Neuroendocrinology·Elizabeth A LawsonJames E Blevins

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