The mechanism of calcitonin gene-related peptide-containing nerve innervation

Calcitonin gene-related peptide (cgrp) is a major neurotransmitter and cgrp-containing primary sensory neurons play an important role in nociception and potent vasodilation. cgrp-containing nerves in mesenteric arteries are decreased in pathological animal models (hypertension,diabetes,and atherosclerosis). in apolipoprotein e-knockout mice,which have atherosclerosis and peripheral sensory nerve defects,nerve growth factor (ngf)-mediated cgrp nerve facilitation was down-regulated,which may have been caused by the impairment of the akt-no-cgmp pathway. in addition,ngf-mediated cgrp neurite outgrowth was decreased in fructose-induced insulin-resistant rats. we recently discovered that renin-angiotensin inhibitors improved cgrp innervation in spontaneously hypertensive rats,indicating that rescuing cgrp nerve innervation might improve pathophysiological conditions. to find a novel reagent that facilitates cgrp nerves,a new model,phenol-injured perivascular nerve model rats,was established. adrenomedullin,hepatocyte growth factor,and angiotensin ii type 2 receptor activation induced cgrp nerve distribution in phenol-injured rats. furthermore,in insulin-resistant model rats,the down-regulation of cgrp nerves was likely due to the depression of phosphoinositide 3-kinase (pi3k)-dependent akt activation. administration of candesartan improves cgrpergic function via the pi3k-akt pathway in insulin-resistant rats. thus,clarification of the mechanisms of cgrp nerve defects may constitute future therapeutic targets. © the japanese pharmacological society.