Cyclic guanosine monophosphate cGMP

Cyclic nucleotide phosphodiesterases (PDEs) are a class of enzymes that catalyze the hydrolysis of 3, 5 -cyclic guanosine monophosphate (cGMP) or 3, 5 -cyclic adenosine monophosphate (cAMP) to 5 -guanosine monophosphate (GMP) or 5 -adenosine monophosphate (AMP), respectively. 

The effect of receptor stimulation is thus to catalyze a reaction cycle. This leads to considerable amplification of the initial signal. For example, in the process of visual excitation, the photoisomerization of one rhodopsin molecule leads to the activation of approximately 500 to 1000 transdudn (Gt) molecules, each of which in turn catalyzes the hydrolysis of many hundreds of cyclic guanosine monophosphate (cGMP) molecules by phosphodiesterase. Amplification in the adenylate cyclase cascade is less but still substantial each ligand-bound P-adrenoceptor activates approximately 10 to 20 Gs molecules, each of which in turn catalyzes the production of hundreds of cyclic adenosine monophosphate (cAMP) molecules by adenylate cyclase. 

Fig. 1. The EDRF/NO pathway in vascular smooth muscle. Vasodilatation by nitrates at a cellular level. Nitrates, nitrites, and nitroprusside-Na are able to release nitric oxide (NO), which stimulates the conversion of GTP into cyclic guanosine monophosphate (cGMP), thus causing vasodilatation. The release of EDRF (=NO) from endothelial cells can be stimulated by various endogenous compounds. Endogenous EDRF (=NO) then causes vasodilatation, similar to the NO released by...

Mechanism of Action An erectile dysfunction agent that inhibits phosphodiesterase type 5, the enzyme responsible for degrading cyclic guanosine monophosphate (cGMP) in the corpus cavernosum of the penis and pulmonary vascular smooth muscle, resulting in smooth muscle relaxation and increased blood flow. Therapeutic Effects Facilitates an erection, produces pulmonary vasodilation. 

Activation of the postsynaptic receptor also leads to activation of the enzymes involved m the formation of so-called second messengers (see Box 42 for explanation of this and other terms used m this section). Best-known second messengers are cychc adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and cleavage products of phosphatidyh-nositol. These molecules are formed at the cell membrane and migrate into the cell where they affect the activity of other enzymes. 

Sildenafil It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction. It results in reduced breakdown of cyclic guanosine monophosphate (cGMP) which is responsible for nitric acid (NO) mediated vasodilatation in corpora cavernosa. Thus inducing an erectile response to sexual stimulation. It has no direct relaxant effect on smooth muscle of corpus cavernosa and has no effect in absence of sexual stimulation. 

GC converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). 4. cGMP causes calcium ions to enter storage areas of the cell. 

B) The pattern of hydroxylation in B-rings is very important for the activity, (i) The absence or the methylation of the hydroxyl group in position 3 accounts for a lower vasodilator potency. In contrast, the lack of the 3 -hidroxyl group is related with a potentiation of the effects in the presence of sodium nitroprusside suggesting a reduced inhibitory effect on cyclic guanosine monophosphate (cGMP) PDE activity, (ii) Morin, with a... 

Sildenafil increases the release of nitric oxide and increases the levels of cyclic guanosine monophosphate (cGMP), a smooth muscle relaxant. Sildenafil enhances the effects of nitric oxide by inhibiting phosphodiesterase 5, an enzyme found primarily in the penis that degrades cGMP. As a result, increased levels of cGMP in the corpus cavemosum enhance smooth muscle relaxation, the inflow of blood, and erection. Sildenafil has no effect in the absence of sexual stimulation (see Figure 60.1). 

Mechanism of action The methylxanthines may act by several mechanisms, including translocation of extracellular calcium, increase in cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) caused by inhibition of phosphodiesterase, and blockade of adenosine receptors. 

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