03.02.3 Cell signaling

Another potential target for drug binding is cell signaling. When endogenous compounds bind to receptors, they initiate cell signaling that leads to the final action of the endogenous compound. Drugs can bind to elements of the cell signaling to enhance or inhibit this process. An example is with cell signaling on bronchial smooth muscle. Adrenaline is the ligand for the β₂-adrenoceptor, and when adrenaline is bound to the receptor, signaling involves activation of adenylyl cyclase (AC) to increase the levels of intracellular cAMP. There is more cell signaling, which eventually leads to relaxation of smooth muscle (bronchodilation) (Figure 3.22).

Figure 3.22 Cell signaling (Copyright QUT, Sheila Doggrell)

The effect of adrenaline stimulation is short-lived, as the action is terminated by the breakdown of cAMP in the presence of the intracellular enzyme phosphodiesterase. Theophylline is a drug that modifies this cell signaling. The mechanism of action of theophylline is to inhibit the phosphodiesterase. The resulting effects is an increased concentration of cAMP and, as cAMP levels dictate the degree of relaxation, increased relaxation of smooth muscle. The clinical use of theophylline is as a bronchodilator in bronchial asthma.