Brain angiotensin receptors and binding proteins

This review addresses classical and novel aspects of the brain angiotensin system. The brain contains both the AT(1) and AT(2) angiotensin II (Ang II) receptor subtypes which are well-characterized guanine nucleotide binding protein (G protein)-coupled receptors (GPCRs). Like other GPCRs, novel signal transduction pathways and protein interactions are being described for Ang II receptors. For brain AT(1) receptors, there is a controversy regarding the identity of the active angiotensin peptide in the brain which is addressed in this review. This review also summarizes a recent discovery of a novel, membrane-bound, non-AT(1), non-AT(2) binding site for angiotensin peptides that appears to be brain-specific. This binding site is unmasked by a limited concentration range of the organometallic sulfhydryl-reactive agent p-chloromercuribenzoic acid (PCMB) suggesting that functional expression of this binding site may depend on the redox state of the milieu of the brain. While this binding site has similarities to a previously described soluble angiotensin-binding protein found in liver that is unmasked by PCMB, it has many different characteristics. The possible functional significance of this novel non-AT(1), non-AT(2) binding site for angiotensin peptides as a mediator of non-traditional actions of Ang II in the brain, e.g., stimulation of dopamine release from the striatum, as a peptidase, or as a clearance receptor, and the importance of the state of the internal environment of the brain to its function is reviewed.