RAMP1 Turns Up the Volume on CGRP in Migraine

HUMAN RECEPTOR ACTIVITY-MODIFYING PROTEIN-1(hRAMP1) may be the switch that turns up the volumeof calcitonin gene-related peptide (CGRP)expression in migraine, according to researchersfrom the University of Iowa in Iowa City.

HUMAN RECEPTOR ACTIVITY-MODIFYING PROTEIN-1(hRAMP1) may be the switch that turns up the volumeof calcitonin gene-related peptide (CGRP)expression in migraine, according to researchersfrom the University of Iowa in Iowa City. "We haveshown that hRAMP1 is a key regulator for theaction of CGRP," the neuropeptide implicated inmigraine expression, reported Andrew Russo, PhD,professor of molecular physiology and biophysicsat the University of Iowa.

Using in vitro neuronal and in vivo transgenicmouse models, the researchers uncovered informationsuggesting that hRAMP1, a normal subunit ofthe CGRP receptor, may be overexpressed inmigraine pathophysiology. Overexpression heightensthe sensitization and responsiveness of CGRPreceptors, which may lead to heightened bloodplasma levels of CGRP and, in turn, the neurogenicinflammatory response characteristic of migraineheadache. Indeed, the researchers showed that neurogenicinflammation in mice engineered to expresshRAMP1 was twice that of the control animals afterbeing injected with CGRP.

Subtle genetic differences in regard to hRAMP1expression may be at play in migraineurs, accordingto Russo. "There is clearly a genetic differencebetween people who get migraines and those whodo not. We think that difference could be RAMP1,"Russo said in a statement to the press. "Our studiesprovide a reason to look for variations in the DNAthat encodes RAMP1 in humans."

For more information on this study, see Zhang Z,Winborn CS, Marquez de Prado B, Russo AF. Sensitizationof calcitonin gene-related peptide receptorsby receptor activity-modifying protein-1 in the trigeminalganglion. J Neurosci. 2007;27:2693-2703.