Distribution of corticotropin‐releasing factor (CRF) receptor binding in the mouse brain using a new,high‐affinity radioligand, [125I]‐PD‐Sauvagine |
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| Authors: | Laura A. Tan Joan M. Vaughan Marilyn H. Perrin Jean E. Rivier Paul E. Sawchenko |
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| Affiliation: | 1. Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, CA;2. Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, CA |
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| Abstract: | The corticotropin‐releasing factor (CRF) family of peptides includes CRF and three urocortins, which signal through two distinct G‐protein coupled receptors, CRF1 and CRF2. Although the cellular distribution of CRF receptor expression has been well characterized at the mRNA level, the localization of receptor protein, and, by inference, of functional receptors, has been limited by a lack of reliable immunohistochemical evidence. Recently, a CRF‐related peptide, termed PD‐sauvagine, was isolated from the skin of the frog, Pachymedusa dacnicolor, and validated as a high‐affinity ligand for CRF receptor studies. A radiolabeled analog, [125I]‐PD‐sauvagine, with high signal‐to‐noise ratio, was used in autoradiographic studies to map the distribution of CRF receptor binding sites in the mouse brain. Through the use of receptor‐deficient mice and subtype‐specific antagonists, CRF1 and CRF2 binding sites were isolated, and found to be readily reconcilable with regional patterns of mRNA expression. Binding site distributions within a given structure sometimes differed from mRNA patterns, however, particularly in laminated structures of the isocortex, hippocampus, and cerebellum, presumably reflecting the trafficking of receptors to their operational homes on neuronal (mostly dendritic) processes. Binding patterns of [125I]‐PD‐sauvagine provided independent assessments of controversial receptor localizations, failing to provide support for CRF1 expression in central autonomic components of the limbic forebrain, the locus coeruleus and cerebellar Purkinje cells, or for CRF2 in any aspect of the cerebellar cortex. Though lacking in ideal resolution, in vitro binding of the PD‐sauvagine radioligand currently provides the most sensitive and accurate available tool for localizing CRF receptors in rodent brain. |
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| Keywords: | corticotropin‐releasing factor G protein‐coupled receptor radioligand binding sauvagine stress urocortin RRID:AB_218182 |
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