Guanylate cyclase receptor system

Nesiritide is a human B-type natriuretic peptide, which binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to dose-dependent reductions in pulmonary capillary wedge pressure and systemic arterial pressure in patients with heart failure. It is indicated in the treatment of patients with acutely decompensated CHF who have dyspnea at rest or with minimal activity. 

Another receptor-enzyme system was elucidated, which forms a guanylate cyclase. This enzyme converts GTP to cGMP upon receptor binding on the outer surface. The resulting cGMP activates either a protein kinase or a phosphodiesterase. 

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

Multicomponent Hormonal Systems Facilitate a Great Variety of Responses The Guanylate Cyclase Pathway Calcium and the Inositol Trisphosphate Pathway Steroid Receptors Modulate the Rate of Transcription... 

Adenylate cyclase is a two-component enzyme system. It ultimately catalyzes the cyclase reaction, but only when it is associated with the hormone-bound receptor and a regulatory protein called a stimulatory G-protein (guanylate nucleotide binding protein), which activates adenylate cyclase. The G-protein is the intermediate between the receptor and the synthesis of cyclic AMP. 

The main signal transduction mechanism for PTH receptor stimulation is the cAMP system. Stimulation of renal or bone PTH receptors causes an elevation of membrane-bound and guanyl nucleotide-dependent adenylate cyclase activity resulting in the enhanced formation of cAMP from ATP. Recent studies suggest that PTH may also stimulate inositol triphosphate and diacylglycerol production in renal tissue (7). 

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