Guanylate cyclase cyclic

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... 

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...

SCHROEDER, H., LEITMAN, D. C., Hayward, L. D., Bennett, B. M., Murphy, F., Cultured rat lung fibroblasts as a model for organic nitrate-induced cyclic GMP accumulation and activation of guanylate cyclase. J. Appl. Cardiol. 2 (1987), p. 301-311... 

Guanylate cyclase converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cyclic GMP). 

Penile erection occurs by relaxation of the smooth muscle of the corpus cavernosum, increasing blood flow into the penis and producing erection and rigidity. In a parallel fashion, vaginal pressure stimulation increases blood velocity and flow into clitoral arteries (Lavoisier et al. 1995). Cavernosal vasodilation is accomplished by neurotransmitters released from the cavernosal nerve and endothelial cells. One of the most important transmitters in this cascade is nitric oxide (NO), which induces synthesis of cyclic GMP from guanylate cyclase (Rajfer et al. 1992). Thus, ginkgo s vascular mechanisms could be responsible for some of the putative sexual effects. 

Changes in the concentration of arginine, via arginase activity, can play a role in regulating the rate of nitric oxide synthesis. Nitric oxide is a messenger molecule that has several roles. One is to increase the activity of the enzyme guanyl cyclase, which increases the concentration of cyclic GMP. The latter causes vasolidation in peripheral... 

An increase in the activity of cyclic GMP phosphodiesterase produces a decrease in the concentration of cyclic GMP only if the activity of the enzyme guanyl cyclase remains constant. The principle underlying this requirement is discussed in Chapter 12,... 

Figure 19.16 Role of nitric oxide synthase in control of penile erection. Nitric oxide synthase catalyses conversion of arginine to nitric oxide, which then acts to acb vate guanyl cyclase which results in an increase in the concentrab on of cyclic GMP. The latter relaxes smooth muscle in the arterioles that supply blood to the corpora cavernosa in the penis so that blood flow increases and erection results.

Fig. 1. Nitric oxide (NO) synthesis by nitric oxide synthase (NOS) (upper left), NO reaction with soluble guanylate cyclase (sGC) (middle), and formation of cyclic GMP, which causes tissue-specific signaling (right). The roles of the salivary nitrophorins from Rhodnius prolixus in storing and releasing NO and binding histamine are included (lower left).

Dark (bottom left). Rod cells that are not exposed to light contain relatively high concentrations (70 pM) of the cyclic nucleotide cCMP (3, 5 -cycloGlVlP cf cAMP, p.386), which is synthesized by a guanylate cyclase ([2], see p.388). The cGMP binds to an ion channel in the rod membrane (bottom left) and thus keeps it open. The inflow of cations (Na, Ca ) depolarizes the membrane and leads to release of the neurotransmitter glutamate at the synapse (see p. 356). 

This enzyme [EC 4.6.1.2], also known as guanylyl cyclase and guanyl cyclase, catalyzes the conversion of GTP to 3, 5 -cyclic GMP and pyrophosphate (or, diphosphate). Both ITP and dGTP can act as substrates. 

Guanylate cyclase, the enzyme that catalyzes the biosynthesis of cyclic GMP from GTP, has been shown to be activated in rat-brain slices by HA, resulting in increased accumulation of cyclic GMP . In addition, HA was demonstrated to possess vasodila-... 

Proposed mechanism by which nitroglycerin and the organic nitrates produce relaxation in vascular smooth muscle. Nitrates induce endothelial cells to release NO or a nitrosothiol (endothelium-derived releasing factor, or EDRF). EDRF activates the enzyme guanylate cyclase, which causes the generation of cyclic guanosine monophosphate (GMP), producing a decrease in cytosolic free calcium. The end result is vascular smooth muscle relaxation. SH, sulfhydryl. 

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... 

Schematic illustration of the interrelationships between glutamate and NO in synaptic function in the cetebellum. The presynaptic nerve terminal synthesizes, stores, and releases glutamate (G) as the neurotransmitter by exocytosis as illustrated. The glutamate diffu.ses across the synaptic cleft and interacts with postsynaptic NMDA recepti>rs ( ) that are coupled to calcium (Ca ) channels. Ca influx occurs and the free intracellular Ca complexes with calmtxlulin and activates NO synthase. NADPH is also required hir conversion, and the products of the reaction are NO plus L-citrulline. NO diffuses out of the piistsynaptic cell to interact with nearby target cells, one of which is the presynaptic neuron that released the glutamate in the first place. NO stimulates cytosolic guanylate cyclase and cyclic GMP (cGMP) formation presynaptically, hut the consequence of this pre.synaptic modification is unknown.

Gruetter, C. A., Barry, B. K., McNamara, D. B., Gruetter, D. Y., Kadowitz, P. J., and Ignarro, L. J. (1979). Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoam-ine. ]. Cyclic Nucleotide Protein Phosphorylation Res. 5, 211-224. 

Ignarro, L. J., Wood, K. S., and Wolin, M. S. (1984d). Regulation of purified soluble guanylate cyclase by porphyrins and metalloporphyrins A unifying concept. Adv. Cyclic Nucleotide Protein Phosphorylation Res. 17, 267-274. 

Mellion, B. T., Ignarro, L. J., Myers, C. B., Ohlstein, E. H., Ballot, B. A., Hyman, A. L., and Kadowitz, P. J. (1983). Inhibition of human platelet aggregation by S-nitrosothiols. Heme-dependent activation of soluble guanylate cyclase and stimulation of cyclic GMP accumulation. Mol. Pharmacol. 23, 653-664. 

Arnold, W. P., Mittal, C. K., Katsuki, S., and Murad, F. (1977). Nitric oxide activates guanylate cyclase and increases guanosine 3 5 -cyclic monophosphate levels in various tissue preparations. Proc. Nad. Acad. Sci. Ll.S.A. 74, 3203-3207. 

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