NDLI: Association of the novel non-AT1, non-AT2 angiotensin binding site with neuronal cell death.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Rashid, Mamoon Arumugam, Thiruma V. Karamyan, Vardan T.
Description	Country affiliation: United States Author Affiliation: Rashid M ( Department of Pharmaceutical Sciences and Vascular Drug Research Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas 79106, USA.)
Abstract	We have discovered a non-AT(1), non-AT(2) angiotensin binding site in rodent and human brain membranes, which, based on its pharmacological/biochemical properties and tissue distribution, is different from angiotensin receptors and key proteases processing angiotensins. In this study, the novel angiotensin binding site was localized to a specific brain cell type by using radioligand receptor binding assays. Our results indicate that the novel binding site is expressed in mouse primary cortical neuronal membranes but not in primary cortical astroglial and bEnd.3 brain capillary endothelial cell membranes. Whole-cell binding assays in neurons showed that the binding site faces the outer side of the plasma membrane. Consistent with our previous observations, the novel binding site was unmasked by the sulfhydryl reagent p-chloromercuribenzoate. This effect had a bell-shaped curve and was reversed by reduced glutathione, indicating that the function of the binding site might be regulated by the redox state of the environment. Density of the novel binding site measured by saturation binding assays was significantly increased in neuronal membranes of cells challenged in four in vitro models of cell death (oxygen-glucose deprivation, sodium azide-induced hypoxia, N-methyl-D-aspartate neurotoxicity, and hydrogen peroxide neurotoxicity). In addition, our in vivo data from developing mouse brains showed that the density of the novel angiotensin binding site changes similarly to the pattern of neuronal death in maturating brain. This is the first time that evidence is provided on the association of the novel angiotensin binding site with neuronal death, and future studies directed toward understanding of the functions of this protein are warranted.
File Format	HTM / HTML
ISSN	00223565
Issue Number	3
Volume Number	335
e-ISSN	15210103
Journal	Journal of Pharmacology and Experimental Therapeutics
Language	English
Publisher	American Society for Pharmacology and Experimental Therapeutics
Publisher Date	2010-12-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Cell Membrane Research Support, Non-u.s. Gov't Temperature Angiotensin Ii Type 2 Receptor Blockers Cytology 4-chloromercuribenzenesulfonate Cerebral Cortex Receptors, Cell Surface Discipline Pharmacology Antagonists & Inhibitors Journal Article Embryology Cell Death Female Physiology Angiotensin Ii Type 1 Receptor Blockers Glutathione P-chloromercuribenzoic Acid Neurons Cell Survival Cells, Cultured 1-sarcosine-8-isoleucine Angiotensin Ii Pharmacology Metabolism Mice, Inbred Strains Drug Effects Prosencephalon Growth & Development Animals Discipline Therapeutics Receptors, Angiotensin Protein Binding Mice Kinetics Angiotensin Ii Subcellular Fractions Glutathione Disulfide
Content Type	Text
Resource Type	Article
Subject	Molecular Medicine Pharmacology

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