Mediation of prolonged increases in nasal mucosal blood flow by calcitonin gene-related peptide (CGRP)

Abstract

Calcitonin gene-related peptide (CGRP) is a vasoactive and smooth muscle contractile neuropeptide, which is released during human nasal allergic reactions. Mean values for nasal blood flow (NBF), quantified in each nostril by a laser Doppler technique, varied no more than ±25% of a mean initial reading in normal human subjects over 4 hr in a controlled environment. Intranasal administration of multiple doses of CGRP to 17 normal subjects stimulated significant mean increases in NBF at 30–1000 ng of CGRP, with maximal mean rises of 86–130% after 100 and 300 ng of CGRP. Delivery of incremental doses of CGRP every 30 min for 2 hr evoked repetitive responses without tachyphylaxis. A single vasoactive dose of CGRP, which achieved nasal fluid concentrations similar to those elicited by antigen challenge, elicited the sensation of nasal obstruction in most subjects at 1 hr and for up to 4 hr after CGRP, without elevating nasal fluid concentrations of histamine. CGRP thus is a potent histamine-independent mediator of allergic reactions.