Biomaterial Database

New Insights into the Regulation of CGRP-Family Receptors. 2019

Joseph J Gingell, and Erica R Hendrikse, and Debbie L Hay

School of Biological Sciences, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand.

The calcitonin gene-related peptide (CGRP) receptor system has emerged as an important drug target for migraine. This is highlighted by the recent regulatory approval of the first drug targeting the CGRP signalling pathway, the CGRP receptor antibody erenumab. The cellular compartments in which receptors are found affects drug access and whether they can exert their effects. G protein-coupled receptors (GPCRs) were thought to signal only at the cell surface, but it is now recognised that some GPCRs, including the CGRP receptor, undergo sustained signalling from endosomes, once internalised in response to ligand. What does this mean for drugs like erenumab? This review covers recent insights into the regulation of CGRP family receptors and examines what implications this may have on drug activity.

UI	MeSH Term	Description	Entries
D008881	Migraine Disorders	A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)	Acute Confusional Migraine,Headache, Migraine,Status Migrainosus,Abdominal Migraine,Cervical Migraine Syndrome,Hemicrania Migraine,Migraine,Migraine Headache,Migraine Variant,Sick Headache,Abdominal Migraines,Acute Confusional Migraines,Cervical Migraine Syndromes,Disorder, Migraine,Disorders, Migraine,Headache, Sick,Headaches, Migraine,Headaches, Sick,Hemicrania Migraines,Migraine Disorder,Migraine Headaches,Migraine Syndrome, Cervical,Migraine Syndromes, Cervical,Migraine Variants,Migraine, Abdominal,Migraine, Acute Confusional,Migraine, Hemicrania,Migraines,Migraines, Abdominal,Migraines, Acute Confusional,Migraines, Hemicrania,Sick Headaches,Variant, Migraine,Variants, Migraine
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077221	Calcitonin Gene-Related Peptide Receptor Antagonists	Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS.	CGRP Receptor Antagonist,CGRP-R Inhibitor,CGRP-R Inhibitors,Calcitonin Gene-Related Peptide Receptor Antagonist,GEPANT,CGRP Receptor Antagonists,GEPANTS,Antagonist, CGRP Receptor,Antagonists, CGRP Receptor,CGRP R Inhibitor,CGRP R Inhibitors,Calcitonin Gene Related Peptide Receptor Antagonist,Calcitonin Gene Related Peptide Receptor Antagonists,Inhibitor, CGRP-R,Inhibitors, CGRP-R,Receptor Antagonist, CGRP,Receptor Antagonists, CGRP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015740	Calcitonin Gene-Related Peptide	A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.	Calcitonin Gene-Related Peptide I,Calcitonin Gene-Related Peptide II,alpha-CGRP,alpha-Calcitonin Gene-Related Peptide,beta-CGRP,beta-Calcitonin Gene-Related Peptide,Calcitonin Gene Related Peptide,Calcitonin Gene Related Peptide I,Calcitonin Gene Related Peptide II,Gene-Related Peptide, Calcitonin,alpha Calcitonin Gene Related Peptide,beta Calcitonin Gene Related Peptide
D043562	Receptors, G-Protein-Coupled	The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.	G Protein Coupled Receptor,G-Protein-Coupled Receptor,G-Protein-Coupled Receptors,G Protein Coupled Receptors,Receptor, G-Protein-Coupled,Receptors, G Protein Coupled
D061067	Antibodies, Monoclonal, Humanized	Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.	Antibodies, Humanized,Humanized Antibodies
D018015	Receptors, Calcitonin Gene-Related Peptide	Cell surface proteins that bind CALCITONIN GENE-RELATED PEPTIDE with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the CENTRAL NERVOUS SYSTEM and the periphery. They are formed via the heterodimerization of the CALCITONIN RECEPTOR-LIKE PROTEIN and RECEPTOR ACTIVITY-MODIFYING PROTEIN 1.	CGRP Receptors,Calcitonin Gene-Related Peptide Receptors,Receptors, CGRP,CGRP Receptor,Calcitonin-Gene Related Peptide Receptor,Calcitonin Gene Related Peptide Receptor,Calcitonin Gene Related Peptide Receptors,Receptors, Calcitonin Gene Related Peptide