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.
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.
von Banchet
Gisela Segond
GS
Jena University Hospital - Friedrich Schiller University Jena, Institute of Physiology Ι, Teichgraben 8, D-07743 Jena, Germany. gban@mti.uni-jena.de
Fischer
Nadja
N
Uhlig
Benjamin
B
Hensellek
Susanne
S
Eitner
Annett
A
Schaible
Hans-Georg
HG
D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology* / Q000187:drug effects*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000235:genetics / Q000378:metabolism*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism
D053583:Interleukin-1beta; D043782:Receptor, Bradykinin B2; D053573:Receptors, Interleukin-1 Type I; D054769:G-Protein-Coupled Receptor Kinase 2; D001920:Bradykinin