Signal Transduction Agonists and Antagonists

A hormone agonist is an analog of the hormone that binds productively to a receptor and mimics the action of the endogenous hormone. An agonist is comparable to an alternative substrate for an enzyme. Because its binding to a receptor is productive; that is, it evokes a metabolic response comparable to that of binding the hormone. By contrast, a hormone antagonist binds to receptors but does not provoke the normal biological response. An antagonist is to a receptor as a competitive inhibitor is to an enzyme; that is, both antagonists and competitive inhibitors compete with a normal ligand (hormone or substrate, respectively) for binding to a specific site on a protein and, by so binding, inhibit a normal biological process.

Agonists and antagonists have been useful in studies of the stereochemistry of binding sites on receptors. In turn, these investigations are useful in drug design, with a goal of activating or inactivating certain classes of receptors. The agonist isoproterenol is used to treat asthma, because it mimics the effects of catecholamines in relaxing bronchial muscles in the lung; it does so by interacting with one specific class of adrenergic receptors (so-called because they bind adrenaline, the old name for epinephrine). Another important drug, used to control blood pressure and pulse rate in cardiac patients, is propranolol, an antagonist of another class of adrenergic receptors, which control blood pressure and heartbeat rate.

Studies of a great many agonists and antagonists of the catecholamines have revealed the existence in vertebrates of four types of catecholamine receptors, each of which has a distinctive pattern of response to these analogs. These are called the 1-, 2-, 1-, and 2-adrenergic receptors (Table 23.3).The structure of the 2-adrenergic receptor is shown in Figure 23.11.

See also: Hormone Action, Action of Epinephrine, Hormone Receptors, G Proteins and Signal Transduction

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