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Antagonists targeting the<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>receptor have been developed and have shown efficacy in clinical trials for migraine. However, no<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>antagonist is yet approved for treating this condition. The molecular composition of the<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>receptor is unusual because it comprises two subunits; one is a<jats:styled-content style=\"fixed-case\">GPCR<\/jats:styled-content>, the calcitonin receptor\u2010like receptor (<jats:styled-content style=\"fixed-case\">CLR<\/jats:styled-content>). This associates with receptor activity\u2010modifying protein (<jats:styled-content style=\"fixed-case\">RAMP<\/jats:styled-content>) 1 to yield a functional receptor for<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>. However,<jats:styled-content style=\"fixed-case\">RAMP1<\/jats:styled-content>also associates with the calcitonin receptor, creating a receptor for the related peptide amylin but this also has high affinity for<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>. Other combinations of<jats:styled-content style=\"fixed-case\">CLR<\/jats:styled-content>or the calcitonin receptor with<jats:styled-content style=\"fixed-case\">RAMPs<\/jats:styled-content>can also generate receptors that are responsive to<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>.<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>potentially modulates an array of signal transduction pathways downstream of activation of these receptors, in a cell type\u2010dependent manner. The physiological significance of these signalling processes remains unclear but may be a potential avenue for refining drug design. This complexity has prompted us to review the signalling and expression of<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>and related receptors in the trigeminovascular system. This reveals that more than one<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>responsive receptor may be expressed in key parts of this system and that further work is required to determine their contribution to<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>physiology and pathophysiology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Neuropeptides. To view the other articles in this section visit<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1111\/bph.2013.170.issue-7\">http:\/\/dx.doi.org\/10.1111\/bph.2013.170.issue\u20107<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12129","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T12:57:56Z","timestamp":1361365076000},"page":"1293-1307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["<scp>CGRP<\/scp>in the trigeminovascular system: a role for<scp>CGRP<\/scp>, adrenomedullin and amylin receptors?"],"prefix":"10.1111","volume":"170","author":[{"given":"C S","family":"Walker","sequence":"first","affiliation":[{"name":"School of Biological Sciences University of Auckland New Zealand"},{"name":"Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D L","family":"Hay","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland New Zealand"},{"name":"Centre for Brain Research University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,14]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/S0022-3565(24)38815-9","article-title":"Pharmacology of SB\u2010273779, a nonpeptide calcitonin gene\u2010related peptide 1 receptor antagonist","volume":"296","author":"Aiyar N","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"issue":"1","key":"e_1_2_14_3_1","first-page":"S1","article-title":"Guide to Receptors and Channels (GRAC), 4th edition","volume":"158","author":"Alexander SP","year":"2009","journal-title":"Br J Pharmacol"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034508330176"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02833.x"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1988.8"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2591.2002.00451.x"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.11.014"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.10.012"},{"key":"e_1_2_14_10_1","unstructured":"BowerRL ValdvogelHJ FaullRLM HayDL(2011).Calcitonin Receptor and receptor activity\u2010modifying protein 1 expression in the human medulla. 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