Like all biologically active molecules, cAMP must be rapidly inactivated for it to function effectively as a second messenger in hormone action. This inactivation is accomplished by phosphodiesterase, an enzyme within the target cells that hy-drolyzes cAMP into inactive fragments. Through the action of phosphodiesterase, the stimulatory effect of a hormone that uses cAMP as a second messenger depends upon the continuous generation of new cAMP molecules, and thus depends on the level of secretion of the hormone.
Bit Drugs that inhibit the activity of phosphodiesterase prevent the breakdown of cAMP and thus result in in-^ creased concentrations of cAMP within the target cells. The drug theophylline and its derivatives, for example, are used clinically to raise cAMP levels within bronchiolar smooth muscle. This duplicates and enhances the effect of epinephrine on the bronchioles (producing dilation) in people who suffer from asthma. Caffeine, a compound related to theo-phylline, is also a phosphodiesterase inhibitor, and thus exerts its effects by raising the cAMP concentrations within cells.
In addition to cyclic AMP, cyclic guanosine monophosphate (cGMP) functions as a second messenger in certain cases. For example, the regulatory molecule nitric oxide (discussed in chapter 7 and later in this chapter) exerts its effects on smooth muscle by stimulating the production of cGMP in its target cells. One example of this is the vascular smooth muscle relaxation that produces erection of the penis (see chapter 20, fig. 20.23). Indeed, as illustrated in this figure, the drug Viagra helps treat erectile dysfunction by inhibiting the phosphodiesterase enzyme that breaks down cGMP.
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