Guanylate cyclase

The ANP leceptoi exists in two forms, ANP and ANPg, both of which have been cloned. These membrane-bound guanylate cyclases have a single transmembrane domain, an intracellular protein kinase-like domain, and a catalytic cyclase domain, activation of which results in the accumulation of cychc guanosine monophosphate (cGMP). A third receptor subtype (ANP ) has been identified that does not have intrinsic guanylate cyclase activity and may play a role in the clearance of ANP. 

A second class of neuronal calcium sensors is formed by the guanylate cyclase-activating protein (GCAP). The GCAPs are expressed only in the photoreceptor cells of the retina of vertebrates. Recoverins and GCAPs have antagonistic roles in phototransduction. 

Figure 13.9 The production and actions of nitric oxide (NO). The influx of calcium through either calcium channels or NMDA receptors triggers NOS to convert L-arginine to NO. L-NAME and 7-NI inhibit this process. NO, once produced, can diffuse in a sphere and then can activate guanylate cyclase...

Acetylcholine-mediated parasympathetic activity leads to production of the non-adrenergic-non-cholinergic transmitter nitric oxide. By enhancing the activity of guanylate cyclase, nitric... 

Lydic, R., Garza-Grande, R., Struthers, R. Baghdoyan, H. A. (2006). Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in cat modulate acetylcholine release in pontine reticular formation. J. Appl. Physiol 100, 1666-73. 

ETEC young children > adults in developing world/travelers to tropics 10-72h acute watery CFA-I-IV - colonization LT-I and -II - adenylate cyclase - secretion STa - guanylate cyclase - secretion STb - cyclic nucleotide-independent HCO] secretion... 

EAggEC children in the developing world 20-48 h persistent FliC - inflammation EAST-1 - guanylate cyclase -t secretion heat-labile toxin Ca2+-dependent actin phosphorylation cytoskeletal damage Pet - histopathologic effects on human intestinal mucosa... 

The Ca2+-calmodulin complex may also activate nitric oxide synthase (NOS), which binds to a PDZ domain of PSD-95. Activated NOS produces NO from arginine NO, in turn, activates guanylate cyclase, the enzyme that catalyzes the conversion of GTP to the intracellular messenger cGMP, which activates protein kinase G (PKG). 

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Guanylate Cyclase Receptors and Biomolecular Targets Involved... 

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. 

Guanylate cyclase signaling pathway also utilizes an enzyme-linked receptor model. The effector enzyme, guanylate cyclase, converts GTP to cGMP, which in turn activates cGMP dependent protein kinase or phosphodiesterases. 

A special guanylate cyclase receptor can be found in the nitric oxide (NO) signaling pathway. The activation of the sequence of events in that pathway results in smooth muscle relaxation. This pathway is directly linked to other cascades by receiving a Ca2+ signal and utilizing calmodulin (CaM) as transmitter protein. 

---