GFL-dependent TRP channel activation and its impact on airway hyperreactivity in asthma

Abstract

Glial cell-line derived growth factor (GDNF) and artemin are neurotrophic factors of the GDNF family of ligands. GDNF binds to its co-receptor GDNF family receptor alpha1 (GFRα1) and artemin to GFRα3. Both signal through the receptor tyrosine kinase RET. Previously, we have shown that GFL-receptors and channels of the transient receptor potential (TRP) family, TRPV1 and TRPA1, are co-expressed in lung-labelled jugular-nodose C-fibers. Even though RET was constitutively expressed in C-fibers, GFRα1 was predominantly expressed in nodose C-fibers (placode-derived), whereas GFRα3 expression was restricted to jugular C-fibers (neural crest-derived). The aim of the study was to compare the effects of GDNF- and artemin-induced RET activation on TRPV1- and TRPA1-function in jugular and nodose C-fibers and to speculate about their role in allergic asthma, which is associated with TRP-channel dysfunction.