Upregulation of G protein-linked receptor kinases with advancing age in rat aorta

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 280; no. 3; pp. 897 - R903
• Main Authors: Schutzer, William E, Reed, John F, Bliziotes, Michael, Mader, Scott L
• Format: Journal Article
• Language: English
• Published: United States 01.03.2001
• Subjects: Aging; Animals; Aorta - enzymology; Aorta - ultrastructure; Arrestins - analysis; Arrestins - metabolism; beta-Adrenergic Receptor Kinases; beta-Arrestin 1; beta-Arrestins; Cell Membrane - enzymology; Cyclic AMP-Dependent Protein Kinases - analysis; Cyclic AMP-Dependent Protein Kinases - metabolism; Cytoplasm - enzymology; G-Protein-Coupled Receptor Kinase 3; G-Protein-Coupled Receptor Kinase 5; Immunoblotting; Isoenzymes - analysis; Isoenzymes - metabolism; Male; Phosphorylation; Protein-Serine-Threonine Kinases - analysis; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Inbred F344; Rhodopsin - metabolism; Vasodilation
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.280.3.r897

1  Portland Veterans Affairs Medical Center, Research Service, Portland 97201 and 2  Oregon Health Sciences University, School of Medicine, Portland, Oregon 97201 The age-related decline in -adrenergic receptor ( -AR)-mediated vasorelaxation is associated with desensitization of -ARs without significant downregulation. The primary mode of this homologous -AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and -arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and -arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and -arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of -ARs. These biochemical changes are consistent with observed aging physiology. -adrenergic receptor kinase; -adrenergic receptor; vasorelaxation