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The neuropeptide calcitonin gene\u2013related peptide (CGRP) is associated with activation of the trigeminovascular system and transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP, it is critical to identify the regions within the brainstem that process CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor\u2013like receptor (CLR) and receptor activity\u2013modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [<jats:sup>3<\/jats:sup>H]MK\u20103207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus, spinal trigeminal nucleus, and spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, and motor trigeminal nucleus; protein coexpression of CLR and RAMP1 was observed in these areas via immunofluorescence. [<jats:sup>3<\/jats:sup>H]MK\u20103207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood\u2013brain barrier, which suggests that drugs inhibiting CGRP signaling may not be able to penetrate the central nervous system to antagonize receptors in these brain regions. J. Comp. Neurol. 524:90\u2013118, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/cne.23828","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T23:37:35Z","timestamp":1435102655000},"page":"90-118","source":"Crossref","is-referenced-by-count":68,"title":["Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence, and autoradiography"],"prefix":"10.1002","volume":"524","author":[{"given":"Sajedeh","family":"Eftekhari","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Division of Experimental Vascular Research Lund University SE\u201022184 Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee C.","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Merck Research Laboratories West Point Pennsylvania 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