Structures that delineate orphanin FQ and dynorphin A pharmacological selectivities.

The Journal of Biological Chemistry
R K ReinscheidO Civelli

Abstract

Strict pharmacological selectivity in families of structurally related ligands and receptors may result from a key process in evolution aiming at increasing diversity in neurotransmission. An intriguing example of such exclusive specificity can be found in the newly discovered orphanin FQ (OFQ) system when it is compared with the opioid system. Both OFQ and its receptor share a high degree of sequence similarity to the opioid peptides and their corresponding receptors, respectively. However, OFQ does not activate opioid receptors, nor do the opioid peptides elicit biological activity at the OFQ receptor. We have therefore investigated the basis for the inherent selectivity of the primary structures of OFQ and dynorphin A, its closest counterpart. A series of truncated and/or chimeric peptides led to the conclusion that both peptides contain domains which establish their pharmacological selectivity. In the OFQ molecule we could delineate a domain that prevents its ability to activate the kappa-opioid receptor by apparently repelling its binding. In both peptides the selectivity-generating domains are composed of single residues in key positions together with short stretches of amino acids which do not overlap. To prove this conc...Continue Reading

References

Jul 1, 1989·Medicinal Research Reviews·V J Hruby, C A Gehrig
Oct 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·C Chavkin, A Goldstein
Dec 15, 1994·Biochemical and Biophysical Research Communications·M NishiT Takeuchi
Mar 17, 1994·Nature·W R MoyleX Wang
Jun 14, 1996·The Journal of Biological Chemistry·R K ReinscheidO Civelli
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·H P NothackerO Civelli
Nov 1, 1996·Neuroscience·J S MogilD K Grandy
Dec 13, 1996·The Journal of Biological Chemistry·F MengH Akil
Aug 1, 1997·Neurochemical Research·M Berthold, T Bartfai

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Citations

Feb 2, 2010·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Benito AntonToby K Eisenstein
Sep 12, 2000·European Journal of Pharmacology·R CiccocioppoM Massi
Feb 26, 2000·European Journal of Pharmacology·J E HawkinsonS A Espitia
Mar 16, 2001·Trends in Neurosciences·O CivelliR K Reinscheid
Mar 26, 1999·Trends in Neurosciences·M G Darlison, D Richter
Jul 26, 2002·Regulatory Peptides·Florian LipplHans Dieter Allescher
Oct 26, 2002·Brain Research. Molecular Brain Research·Deepak R Thakker, Kelly M Standifer
Sep 22, 2000·Peptides·G Calo'D Regoli
Sep 22, 2000·Peptides·C PolidoriM Massi
Sep 22, 2000·Peptides·R CiccocioppoM Massi
Feb 12, 2002·Peptides·Andrzej RubajMaria Sieklucka-Dziuba
Mar 8, 2000·Peptides·L M Harrison, D K Grandy
Aug 2, 2008·Nature Reviews. Drug Discovery·David G Lambert
Jan 25, 2012·International Journal of Molecular Sciences·Pingping BaoLing Yang
Nov 6, 2013·Pharmacology & Therapeutics·Jeffrey M WitkinRoberto Ciccocioppo
Nov 5, 2013·Progress in Neuro-psychopharmacology & Biological Psychiatry·Francesca Felicia CaputiPatrizia Romualdi
Dec 23, 2009·Hormones and Behavior·Annabell C SegarraYvonne M Torres-Diaz
Dec 12, 2007·British Journal of Pharmacology·S ChungO Civelli
Jan 26, 2010·Medicinal Research Reviews·Carlo Mustazza, Giuditta Bastanzio
Aug 29, 2006·Brain Research·Soochuen T KhoGail Ishiyama
Nov 18, 2005·Pharmacology & Therapeutics·Olivier CivelliRainer K Reinscheid
Mar 20, 1999·General and Comparative Endocrinology·P B Danielson, R M Dores

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