Desensitization of G-protein-coupled receptors in the cardiovascular system

Multiple mechanisms exist to control the signaling and density of G-protein -coupled receptors (GPRs). Upon agonist binding and receptor activation, a series of reactions participate in the turn off or desensitization of GPRs. Many GPRs are phosphorylated by protein kinases and consequently uncoupled from G proteins. In addition, many GPRs are sequestered from the cell surf ace and become inaccessible to their activating ligands. Both receptor:G pr otein uncoupling and receptor sequestration may involve the participation o f arrestins or other proteins. A model for receptor regulation has been dev eloped from studies of the beta-adrenergic receptor. However, recent studie s suggest that other GPRs important in the cardiovascular system, such as t he muscarinic cholinergic receptors that regulate heart rate, might be regu lated by mechanisms other than those that regulate the beta-adrenergic rece ptors. This review summarizes our current understanding of the processes in volved in the desensitization of GPRs.