Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia

Abstract

In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.

Angiotensin‐converting enzyme inhibition reduces oxidative stress and protects dopaminergic neurons in a 6‐hydroxydopamine rat model of Parkinsonism

“…The brain possesses a local angiotensin system (Gendron et al, 2003;McKinley et al, 2003;Pan, 2004;Rodriguez-Pallares et al, 2004), and the results of previous studies have suggested that AII and its receptors play an important role in modulating striatal dopamine (DA) levels. Both AII and AII receptors as well as angiotensinogen and angiotensin-converting enzyme (ACE) have been observed in the striatum (Quinlan and Phillips, 1981;Brownfield et al, 1982;Chai et al, 1987;Allen et al, 1992Allen et al, , 1998, and AII stimulates the release of newly synthesized DA via angiotensin type 1 receptors (AT 1 ) located in the striatal DA terminals (Mendelsohn et al, 1993;Brown et al, 1996;Ge and Barnes 1996). However, it has recently been shown that in several cell types, including neurons, reactive oxygen species (ROS) play a crucial role in the signaling of AII via AT 1 receptors.…”

Angiotensin Receptor Subtypes and their Pharmacology

“…A fuller account of Ang II receptors in the human brain has been published [48][49][50]. The high density of Ang II receptors in the substantia nigra occurs over pigmented, presumably dopaminergic, neurons [51]. The binding in this site, and in the striatum, is not observed in any of the other species we have studied.…”

ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone

“…Both ACE and angiotensin receptors were identified in dopaminergic neurons of basal ganglia (Allen et al, 1992). Significant decreased dopamine release determined by ACE inhibitors was also demonstrated (Obata et al, 2008).…”