3 ,5 -Cyclic guanylate

Acetylcholine works with other neurotransmitters (i.e., cyclic guanylate monophosphate, cyclic adenosine monophosphate, vasoactive intestinal polypeptide) to produce penile arterial vasodilation and ultimately an erection. 

Phosphodiesterase mediates catabolism of cyclic guanylate monophosphate, a vasodilatory neurotransmitter in the corporal tissue. 

FIGURE 14-4. Once formed, nitric oxide activates the enzyme guanylyl cyclase (GC) by binding to iron (heme) in the active site of this enzyme. When activated, GC makes a messenger, (cyclic guanylate monophosphate (cGMP), which relaxes smooth muscle and performs other physiological functions. In the penis, relaxation of vascular smooth muscle opens blood flow and causes an erection. 

The intracellular enzyme associated with some types of receptor that on activation produces the secondary messenger cyclic guanylate monophosphate (cyclic GMP). 

The penis has two corpora cavernosa, which have many interconnected sinuses that fiU with blood to produce an erection. The penis also has one corpus spongiosum, which surrounds the urethra and forms the glans penis. Acetylcholine works with other neurotransmitters (i.e., cyclic guanylate monophosphate, cyclic adenosine monophosphate, vasoactive intestinal polypeptide) to produce penile arterial vasodilation and ultimately an erection. Causes of organic ED include diseases that compromise vascular flow to the corpora cavernosum (e.g., peripheral vascular disease, arteriosclerosis, essential hypertension), impair nerve conduction to the brain (e.g., spinal cord injury, stroke), and are associated with hypogonadism (e.g., prostate or testicular cancer, hypothalamic or pituitary disorders). 

A vasodilator would have a slightly delayed effect, due to the processes involved in smooth muscle relaxation. If this drug were a nitrate, such as amyl nitrate, effects would be immediate, because the nitrate is converted almost instantly by the vascular endothelium into nitric oxide (NO), which increases levels of cyclic guanylate monophosphate (cGMP) and mediates vasodilatation within seconds. 

Endothelial, neuronal, mitochondrial, and inducible (iNOS) forms belong to the NOS family, whose activities are based on NADPH and calmodulin (Rios-Arrabal et al., 2013). eNOS modulates cancer-related processes, such as cell death, angiogenesis, and invasion, so it possesses signi cant importance in tumor development. Cyclic guanylate monosphosphate and guanylyl cyclase mediate many biochemical reactions of nitric oxide (Miguel, 2010 Rios-Arrabal et al., 2013) (Table 11.2). 

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... 

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. 

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