The renin-angiotensin system (RAS) was initially considered as a circulating humoral system, which function is the regulation of blood pressure. However, it is now known that there exists local RAS in many tissues, including brain. In recent studies, we have demonstrated the presence of a local RAS in the substantia nigra of rodents and primates that modulates dopamine release and dopamine receptor expression. However, overactivation of local RAS exacerbates neuroinflammation, oxidative stress and dopaminergic cell death. In the striatum, it is not clear whether angiotensin receptors are located in dopaminergic terminals, glial cells and/or the projection neurons. The present study shows the location of major components of the RAS in striatal projection neurons of rats and monkeys (both in neurons of the direct and the indirect pathways). Striatal astrocytes and microglial cells also express major RAS components, which increase after induction of neuroinflammation by intrastriatal injection of lipopolysaccharide. Angiotensin receptors were located at the cell surface and also at cytoplasmic and nuclear levels. The results obtained by immunolabeling and confocal microscopy were confirmed with laser microdissection of striatal neurons and glial cells and detection of mRNA expression by PCR. The sequence of the resulting PCR products was verified by DNA sequencing. In addition to the interaction between angiotensin and dopamine receptors in dopaminergic neurons to regulate dopamine release, interaction between angiotensin and dopamine receptors in projection striatal neurons may further modulate the effects of dopamine on the direct and indirect pathways by fine-tuning striatal dopaminergic neurotransmission.
Keywords: Angiotensin; Basal ganglia; Dopamine; Neurodegeneration; Parkinson; Striatum.