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Distribution of corticotropin‐releasing factor (CRF) receptor binding in the mouse brain using a new, high‐affinity radioligand, [ 125 I]‐PD‐Sauvagine
Author(s) -
Tan Laura A.,
Vaughan Joan M.,
Perrin Marilyn H.,
Rivier Jean E.,
Sawchenko Paul E.
Publication year - 2017
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.24307
Subject(s) - biology , receptor , radioligand , urocortin , medicine , cerebellum , endocrinology , forebrain , locus coeruleus , neuroscience , microbiology and biotechnology , central nervous system , biochemistry
The corticotropin‐releasing factor (CRF) family of peptides includes CRF and three urocortins, which signal through two distinct G‐protein coupled receptors, CRF 1 and CRF 2 . 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, [ 125 I]‐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, CRF 1 and CRF 2 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 [ 125 I]‐PD‐sauvagine provided independent assessments of controversial receptor localizations, failing to provide support for CRF 1 expression in central autonomic components of the limbic forebrain, the locus coeruleus and cerebellar Purkinje cells, or for CRF 2 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.