11-cis-retinal and Arthritis--Rheumatoid

G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptors (GPCRs) to effect receptor phosphorylation and to initiate profound impairment of receptor signalling, or desensitization. GPCRs form the largest family of cell surface receptors known and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations. This review focuses on the physiological role of GRKs revealed by genetically modified animals but also develops the involvement of GRKs in human diseases as, Oguchi disease, heart failure, hypertension or rhumatoid arthritis. Furthermore, the regulation of GRK levels in opiate addiction, cancers, psychiatric diseases, cystic fibrosis and cardiac diseases is discussed. Both transgenic mice and human pathologies have demonstrated the importance of GRKs in the signalling pathways of rhodopsin, beta-adrenergic and dopamine-1 receptors. The modulation of GRK activity in animal models of cardiac diseases can be effective to restore cardiac function in heart failure and opens a novel therapeutic strategy in diseases with GPCR dysregulation.

Topics: Animals; Arthritis, Rheumatoid; Cell Membrane; Cyclic AMP-Dependent Protein Kinases; Heart Diseases; Humans; Hypertension; Mice; Mice, Transgenic; Models, Biological; Neoplasms; Phosphorylation; Protein Kinases; Receptors, Adrenergic, beta; Receptors, Dopamine; Receptors, G-Protein-Coupled; Rhodopsin; Signal Transduction

Fourteen patients with rheumatoid arthritis were tested for the presence of cell-mediated immune reactivity to various ocular antigens by means of the leucocyte migration inhibition test. A significant difference in leucocyte migration was found between patients and healthy controls after incubation of their cells with purified rhodopsin, uveal pigment granules or soluble uveal antigens, but not with rod outer segments or soluble retinal antigens. Some indications have been obtained that the sensitization to rhodopsin in fact originates from a sensitization to connective tissue structural glycoproteins.

Topics: Adult; Aged; Antigens; Arthritis, Rheumatoid; Connective Tissue; Eye; Glycoproteins; Humans; Immunity, Cellular; Leukocyte Migration-Inhibitory Factors; Middle Aged; Retinal Pigments; Rhodopsin