125 I-Antisauvagine-30: a novel and specific high-affinity radioligand for the characterization of corticotropin-releasing factor type 2 receptors

125 I-Antisauvagine-30: a novel and specific high-affinity radioligand for the characterization... Corticotropin-releasing factor (CRF) receptors type 1 (CRF 1 ) and type 2 (CRF 2 ) differ from each other in their pharmacological properties. The human and ovine CRF versions bind to CRF 1 receptors with significantly higher affinity than to CRF 2 receptors. Recently antisauvagine-30, an N-terminally truncated version of the CRF analog sauvagine, was characterized as a specific antagonist to mouse CRF 2B . We have synthesized the radiolabeled version 125 I-antisauvagine-30 and tested it for its affinity at human CRF 1 (hCRF 1 ), hCRF 2A , Xenopus CRF 1 (xCRF 1 ) and xCRF 2 receptors. In control binding studies 125 I-labeled hCRF, sauvagine and astressin were also bound to these receptors. 125 I-antisauvagine-30 exclusively bound to hCRF 2A and xCRF 2 but not to hCRF 1 and xCRF 1 receptors. 125 I-antisauvagine-30 binding to hCRF 2A and xCRF 2 receptors was saturable and of high affinity (hCRF 2A : K d =125 pM; xCRF 2 : K d =1.1 nM). In displacement binding experiments using 125 I-antisauvagine-30 as radioligand several CRF analogs bound to hCRF 2A and xCRF 2 receptors with similar rank orders as reported with other CRF radioligands. Finally, preliminary studies using 125 I-antisauvagine-30 binding to membrane homogenates prepared from different rat brain structures showed that the peptide bound specifically to brain areas expressing CRF 2 receptors. These data demonstrate that 125 I-antisauvagine-30 is the first high-affinity ligand to specifically label CRF 2 receptors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

125 I-Antisauvagine-30: a novel and specific high-affinity radioligand for the characterization of corticotropin-releasing factor type 2 receptors

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(00)00105-2
Publisher site
See Article on Publisher Site

Abstract

Corticotropin-releasing factor (CRF) receptors type 1 (CRF 1 ) and type 2 (CRF 2 ) differ from each other in their pharmacological properties. The human and ovine CRF versions bind to CRF 1 receptors with significantly higher affinity than to CRF 2 receptors. Recently antisauvagine-30, an N-terminally truncated version of the CRF analog sauvagine, was characterized as a specific antagonist to mouse CRF 2B . We have synthesized the radiolabeled version 125 I-antisauvagine-30 and tested it for its affinity at human CRF 1 (hCRF 1 ), hCRF 2A , Xenopus CRF 1 (xCRF 1 ) and xCRF 2 receptors. In control binding studies 125 I-labeled hCRF, sauvagine and astressin were also bound to these receptors. 125 I-antisauvagine-30 exclusively bound to hCRF 2A and xCRF 2 but not to hCRF 1 and xCRF 1 receptors. 125 I-antisauvagine-30 binding to hCRF 2A and xCRF 2 receptors was saturable and of high affinity (hCRF 2A : K d =125 pM; xCRF 2 : K d =1.1 nM). In displacement binding experiments using 125 I-antisauvagine-30 as radioligand several CRF analogs bound to hCRF 2A and xCRF 2 receptors with similar rank orders as reported with other CRF radioligands. Finally, preliminary studies using 125 I-antisauvagine-30 binding to membrane homogenates prepared from different rat brain structures showed that the peptide bound specifically to brain areas expressing CRF 2 receptors. These data demonstrate that 125 I-antisauvagine-30 is the first high-affinity ligand to specifically label CRF 2 receptors.

Journal

NeuropharmacologyElsevier

Published: Jan 1, 2001

References

  • N-Terminal splice variants of the type I PACAP receptor: isolation, characterization, and ligand binding/selectivity determinants
    Dautzenberg, F.M.; Mevenkamp, G.; Wille, S.; Hauger, R.L.
  • Functional characterization of corticotropin-releasing factor type 1 receptor endogenously expressed in human embryonic kidney 293 cells
    Dautzenberg, F.M.; Higelin, J.; Teichert, U.
  • Labelling of CRF 1 and CRF 2 receptors using the novel radioligand ( 3 H)-urocortin
    Gottowik, J.; Goetschy, V.; Henriot, S.; Kitas, E.; Fluhmann, B.; Clerc, R.G.; Moreau, J.L.; Monsma, F.J.; Kilpatrick, G.J.
  • The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety
    Holsboer, F.
  • Isolation and pharmacological characterization of two functional splice variants of corticotropin-releasing factor type 2 receptor from Tupaia belangeri
    Palchaudhuri, M.R.; Hauger, R.L.; Wille, S.; Fuchs, E.; Dautzenberg, F.M.

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