title: Brain angiotensin receptors and binding proteins.
abstract: This review addresses classical and novel aspects of the brain angiotensin system. The brain contains both the AT1 and AT2 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 AT1 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-AT1, non-AT2 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-AT1, non-AT2 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.
authors.affiliation: Department of Pharmacology, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, Oxford, MS 38677, USA. Speth@Olemiss.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Speth
authors.forename: Vardan T
authors.initials: VT
authors.lastname: Karamyan
mesh_terms: D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D011485:Protein Binding; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism
chemical_list: D000809:Angiotensins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II