IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cutaneous inflammation differently regulates the expression and function of angiotensin II types 1 and 2 receptors in rat primary sensory neurons
Autor/es:
DIEGO MESSINA; MABEL FOSCOLO; SERGIO BENITEZ; SEAN PATTERSON; ALICIA SELTZER; CRISTIAN ACOSTA
Lugar:
Mendoza
Reunión:
Simposio; II International Symposium on Translational Medicine; 2019
Institución organizadora:
UNCuyo/UN Freiburg/UBA
Resumen:
AbstractIntroduction and objectivesCellular and molecular changes that affect the excitability of dorsal root ganglion (DRG) neurons underlie neuropathic and inflammatory pain. Amongst others, the type 2 receptor for Angiotensin-II (AT2R) has been involved in this type of pain. However, the underlying mechanisms are poorly understood as is the role of the Angiotensin-II type 1 receptor (AT1R) in these processes. Thus, we examined how cutaneous inflammation affected the expression of AT1R and AT2R in rat DRG and also the impact of their pharmacological manipulation on inflammation-induced neuritogenesis. MethodsWe used immunohistochemistry, immunocytochemistry, semi-quantitative RT-PCR and selective AT1R and AT2R antagonists to examine their involvement in axonal growth and branching in normal and inflammatory conditions (both in vivo and in vitro). We also tested in vivo neuritogenesis in nociceptors innervating the skin.ResultsPhenotypic characterization using IB4, trkA, NF200 and substance-P demonstrated that AT2R-expressing neurons were C- and Aδ-nociceptors. AT1R was found in all neuronal sizes with higher levels in small neurons and its expression correlated significantly and positively with AT2R. In vitro, an inflammatory soup caused significant elevation of AT2R mRNA while AT1R mRNA levels remained unchanged. In vivo, cutaneous inflammation affected AT1R and AT2R expression in different DRG subpopulations at different times. AT2R increased in small neurons at 1 day and in medium size neurons at 4 days. Interestingly, cutaneous inflammation increased AT1R levels only in large neurons at 4 days. We found also that in vitro and in vivo AT1R and AT2R acted in concert to regulate DRG neurite outgrowth. In vivo, AT2R seemed more relevant for non-peptidergic C-nociceptor neuritogenesis while AT1R was more prominent in peptidergic nerve terminals. Conclusions In DRG neurons that respond to inflammation the key is the balance between the expression and activity of both receptors rather than their mutual antagonism.