Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I, thereby reducing reperfusion-induced apoptosis in mice.
Calcitonin gene-related peptide (CGRP) increases insulin-like growth factor-I (IGF-I) production in fetal rat osteoblasts in vitro, suggesting that stimulation of sensory neurons might increase IGF-I production, thereby preventing apoptosis. We examined whether stimulation of sensory neurons by capsaicin might reduce reperfusion-induced hepatic apoptosis by increasing IGF-I production. Administration of capsaicin increased tissue levels of IGF-I and IGF-I mRNA in various organs in wild-type (WT) mice, but not in CGRP-knock-out (CGRP-/-) mice. Administration of CGRP increased tissue levels of IGF-I and IGF-I mRNA in both WT and CGRP-/- mice. Increases in hepatic tissue levels of TNF, serum levels of transaminases, hepatic apoptosis and hepatic tissue levels of caspase-3 after hepatic ischemia/reperfusion (I/R) were more marked in CGRP-/- mice than in WT mice. Hepatic IGF-I levels were increased in WT mice after reperfusion, while they were not changed in CGRP-/- mice. Although administration of capsaicin enhanced increases in IGF-I levels and reduced reperfusion-induced events in WT mice, it had no effect in CGRP-/- mice. Administration of CGRP and IGF-I reduced reperfusion-induced effects in both strains of mice. These observations suggested that capsaicin-induced sensory neuron activation, which leads to release of CGRP, might increase IGF-I production, thereby reducing reperfusion-induced liver injury by reducing apoptosis.
Harada
Naoaki
N
Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Okajima
Kenji
K
Kurihara
Hiroki
H
Nakagata
Naomi
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D005838:Genotype; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015427:Reperfusion Injury / Q000473:pathology*; D013268:Stimulation, Chemical
D007202:Indicators and Reagents; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D053148:Caspase 3; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin