Hormone Analogs Are Widely Used as Drugs

Synthetic analogs of natural hormones are widely used both in research on cell-surface receptors and as drugs. These analogs fall into two major classes. Agonists mimic the function of a natural hormone by binding to its receptor and inducing the normal cellular response to the hormone. Many synthetic agonists bind much more tightly to the receptor than does the natural hormone. In contrast, antagonists bind to the receptor but induce no response. By occupying ligand-binding sites on a receptor, an antagonist can block binding of a natural hormone (or agonist) and thus reduce the usual physiological activity of the hormone. In other words, antagonists inhibit receptor signaling.

Consider, for instance, the drug isoproterenol, used to treat asthma. Isoproterenol is made by the chemical addition of two methyl groups to epinephrine (Figure 15-9). Isoproterenol, an agonist of β2 epinephrine-responsive G protein–coupled receptors on bronchial smooth muscle cells, binds about tenfold more strongly (has a tenfold lower Kd) than does epinephrine. Because activation of these receptors promotes relaxation of bronchial smooth muscle and thus opening of the air passages in the lungs, isoproterenol and other agonists are used in treating bronchial asthma, chronic bronchitis, and emphysema. In contrast, activation of a different type of epinephrine-responsive G protein–coupled receptor on cardiac muscle cells (called the β1-adrenergic receptor) increases the heart contraction rate. Antagonists of this receptor, such as alprenolol (see Figure 15-9) and related compounds, are referred to as beta-blockers; such antagonists are used to slow heart contractions in the treatment of cardiac arrhythmias and angina.

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FIGURE 15-9 Structures of the natural hormone epinephrine, the synthetic agonist isoproterenol, and the synthetic antagonist alprenolol. As discussed in the text, isoproterenol and alprenolol, both of which bind to receptors for epinephrine, are used as drugs to treat different conditions.