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&ndash;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&ndash;NO&ndash;cGMP pathway. In addition, NGF-mediated CGRP neurite outgrowth was decreased in fructose-induced insulin-resistant rats. We recently discovered that renin&ndash;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&ndash;Akt pathway in insulin-resistant rats. Thus, clarification of the mechanisms of CGRP nerve defects may constitute future therapeutic targets.
Department of Life Science, Okayama University of Science, Okayama, Japan. hobara@dls.ous.ac.jp
Narumi
N
Hashikawa-Hobara
Naoya
N
Hashikawa
Yoshito
Y
Zamami
Shingo
S
Takatori
Hiromu
H
Kawasaki
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology*; D004195:Disease Models, Animal; D005632:Fructose; D006937:Hypercholesterolemia; D006973:Hypertension; D007333:Insulin Resistance; D008638:Mesenteric Arteries / Q000294:innervation; D051379:Mice; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000139:chemically induced / Q000503:physiopathology*; D019800:Phenol; D051381:Rats; D011984:Sensory Receptor Cells / Q000502:physiology
D005632:Fructose; D019800:Phenol; D015740:Calcitonin Gene-Related Peptide