CHARACTERIZATION OF THE ANGIOTENSIN TYPE 1 RECEPTOR AND THE BETA2 ADRENERGIC RECEPTOR PROPERTIES: THE INVOLVEMENT OF ARRESTIN2, RAB1 AND SOME MOLECULAR CHAPERONES IN THE ASSEMBLY AND TRAFFICKING OF GPCRS
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Current drugs used to treat Congestive Heart Failure target the renin-angiotensin and adrenergic systems. Studies showed increased mortality rates in patients treated with a combination of these medications. Angiotensin-AT1 and ?2-Adrenergic receptors were shown to form receptor heteromers. Blockade of one receptor in the complex can affect the signal transmitted by the other; suggesting that ligand-based therapy is not as selective as we might think. Modulating receptor trafficking after synthesis might prove to be a valid therapeutic strategy. Unfortunately, little is known about receptor assembly and transport from Endoplasmic Reticulum to Plasma Membrane. The objectives of this study are to identify the proteins that participate in the assembly of AT1R-?2AR heteromer and the regulators of the anterograde trafficking of G-Protein Coupled Receptors. This thesis introduces the role of important targets in those poorly understood processes. The identification of such targets could lead to developing better drugs with fewer adverse effects.
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