Molecular effects of interleukin-1β on dorsal root ganglion neurons: prevention of ligand-induced internalization of the bradykinin 2 receptor and downregulation of G protein-coupled receptor kinase 2

Abstract

In dorsal root ganglion sections numerous small-to medium-sized neurons were found to exhibit extensive colocalization of the bradykinin receptor 2, the interleukin-1 receptor 1 and G protein-coupled receptor kinase 2. Application of bradykinin to cultured DRG neurons caused substantial internalization of the bradykinin 2 receptor which significantly reduced the responsiveness of DRG neurons to a second application of bradykinin. Such an internalization was not observed in DRG neurons which were exposed to long-term pretreatment with interleukin-1β. The long-term incubation with interleukin-1β on its own did neither change the proportion of neurons which expressed the bradykinin 2 receptor in the cytoplasma nor the proportion of neurons expressing the bradykinin 2 receptor in the membrane but it reduced the proportion of neurons expressing G protein-coupled receptor kinase 2, an enzyme which facilitates the internalization of G protein-coupled receptors. These results show that interleukin-1β maintains the responsiveness of DRG neurons to bradykinin in the long-term range, and they suggest that the downregulation of G protein-coupled receptor kinase 2 could be a cellular mechanism involved in this interleukin-1β effect.