Phosphodiesterase type 5 PDE

As long as the couple are not stressed by the sexual position they use, there is no evidence of increased cardiac stress to a man or woman. Man on top, woman on top, side to side, oral sex, and masturbation are cardiologically equivalent. In homosexual relationships, other than casual, anal intercourse is not associated with increased cardiac stress provided proper lubrication is used and amyl nitrate ( poppers ) are not used in the presence of a phosphodiesterase type-5 (PDE-5) inhibitor by the patient or partner. 

Fig. 1.15 Structure of the phosphodiesterase type 5 (PDES) inhibitor sildenafil [25,26].

The erectile dysfunction group of drugs, of which sildenafil is most common, are potent inhibitors of cyclic guanosine monophosphate-specific phosphodiesterase type 5 (PDE-5). The other two available drugs are tadalafil (Cialis) and... 

Sildenafil (Viagra ), tadalafil (Cialis ), and vardenafil (Levitra ) act by selectively inhibiting phosphodiesterase (PDE) type 5, an enzyme that breaks down cGMP. By inhibiting the breakdown of cGMP, smooth muscle relaxation is... 

It is a relatively selective inhibitor of cyclic GMP, cyclic AMP-PDE (phosphodiesterase) type 111 family. It causes vasodilatation with a consequent decrease in systemic vascular resistance. It increases both the force of contraction and velocity of relaxation of cardiac muscles. It is administered IV 0.75 mg/kg/min as a bolus dose followed by 5-10 pg/kg/min IV infusion and total dose not to exceed 10 mg/kg. 

FIGURE 14—5. The action of cGMP is terminated by the enzyme phosphodiesterase. In the penis, the type of phosphodiesterase is type V (PDE V). 

It was mentioned earlier that the expression of HIV protease within E. coli gives rise to a phenotype, hi a similar fashion, it has been observed that phosphodiesterases (PDEs) when expressed in yeast affect the cells. These enzymes function to modulate intracellular concentrations of the cyclic mononucleotides cAMP or cGMP Yeast has two endogenous genes encoding PDEs which, when deleted, lead to elevated levels of cAMP within the ceU. The consequence to the yeast of elevated cAMP is increased sensitivity to heat shock and inability to utilize acetate as sole carbon source. These yeast mutants may be complemented by the human PDE gene and the phenotype reversed (Eigure 5.5). The use of such yeast in the search for inhibitors of PDEs with utility in, for example, asthma has been proposed" and certainly works with the known type IV PDEs inhibitor, rolipram. 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

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