Intraneuronal angiotensinergic system in rat and human dorsal root ganglia

Abstract

To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)-and cathepsin D-mRNA, and the presence of protein renin, Ang II, Substance P and calcitonin gene-related peptide (CGRP) in the rat and human thoracic DRG. Quantitative real time PCR (qRT-PCR) studies revealed that rat DRG expressed substantial amounts of Ang-N-and ACE mRNA, while renin mRNA as well as the protein renin were untraceable. Cathepsin D-mRNA and cathepsin D-protein were detected in the rat DRG indicating the possibility of existence of pathways alternative to renin for Ang I formation. Angiotensin peptides were successfully detected with high performance liquid chromatography and radioimmunoassay in human DRG extracts. In situ hybridization in rat DRG confirmed additionally expression of Ang-N mRNA in the cytoplasm of numerous neurons. Intracellular Ang II staining could be shown in number of neurons and their processes in both the rat and human DRG. Interestingly we observed neuronal processes with angiotensinergic synapses en passant, colocalized with synaptophysin, within the DRG. In the DRG, we also identified by qRT-PCR, expression of Ang II receptor AT 1A and AT 2 -mRNA while AT 1B -mRNA was not traceable. In some neurons Substance P and CGRP were found colocalized with Ang II. The intracellular localization and colocalization of Ang II with Substance P and CGRP in the DRG neurons may indicate a participation and function of Ang II in the regulation of nociception. In conclusion, these results suggest that Ang II may be produced locally in the neurons of rat and human DRG and act as a neurotransmitter.

The Characterization of AT1 Expression in the Dorsal Root Ganglia After Chronic Constriction Injury

“…RT-PCR using specific primers and emulsion autoradiography of the hybridized DRG sections with selective riboprobes revealed the presence of AT 1 mRNA in the rat DRG (Patil et al 2010;Pavel et al 2008). Similarly, our immunofluorescence results have shown that AT 1 is expressed in different extent to most of the DRG neuronal cells.…”

“…Recently, the presence of intraneuronal angiotensinergic system and Angiotensin II receptor type 1 (AT 1 ) has been documented in rat dorsal root ganglia (DRGs) (Patil et al 2010;Pavel et al 2008;Tang et al 2008), the structures containing primary afferent neurons that convey sensory information from periphery to the CNS. Our previous study showed that AT 1 binding and mRNA, determined by in situ hybridization with specific riboprobes, are localized to numerous neuronal cells in the DRGs .…”

Involvement of Spinal Angiotensin II System in Streptozotocin-Induced Diabetic Neuropathic Pain in Mice

“…Although chymase can form Ang II by cleaving Ang I (Kirimura et al, 2005), its mRNA was also absent from the lumbar dorsal spinal cord. Similar to the spinal cord, the mRNA for cathepsin D, but not renin, is reported to be expressed in the DRG (Patil et al, 2010). Therefore, we can speculate that cathepsin D cleaves AGT to Ang I, which is in turn converted to Ang II by ACE in the spinal cord.…”

“…In both rat and human dorsal root ganglia (DRGs) Ang II is colocalized in two known regulators for nociception and sensory transmission: substance P and calcitonin gene-related peptide (Patil et al, 2010). We have previously demonstrated that when mice are administered Ang II intrathecally, p38 mitogenactivated protein kinase (MAPK) is phosphorylated through AT1 receptors, leading to nociceptive behavior (Nemoto et al, 2013(Nemoto et al, , 2015a.…”

Le cophénotype sympathique efférent des fibres autonomes angiotensinergiques dans le cœur humain

“…Il transmet par l'Ang II un effet vasoconstricteur au niveau des vaisseaux médié par ses récepteurs AT 1 . Grâce à l'utilisation d'un anticorps monoclonal hautement spécifique (Mab 4B3) et une méthodologie immunocytologique adaptée, nous avons réussi à dépister un sous-groupe de neurones avec un phénotype Ang II-positif parmi les neurones du ganglion céliaque, trigé-minal et spinal chez le rat comme chez l'homme [4][5][6]. Nous avons également retrouvé un phénotype Ang II-positif parmi les fibres autonomes innervant le coeur, les artères et le rein dans plusieurs espèces (rat, cochon et homme) [4,7,8].…”