produced by bacteria such as Staphylococcus aureus respond to antibiotics such as
penicillin. Penicillin binds to “exogenous receptors” located on the bacterium.
2.10 RECEPTOR ACTION: MECHANISMS IN RECEPTOR
SIGNAL TRANSDUCTION
From the genome sequence of humans and other organisms deduced in the past several
years, it is now appreciated that there are literally thousands of different receptors.
However, it is likewise appreciated that Nature is efficient and has organized these thou-
sands of receptors into a mere handful of “superfamilies.” One of these superfamilies
consists of the voltage-gated ion channels. Recent work by MacKinnon and co-workers
has provided groundbreaking structural data on this superfamily. Another, and probably
more important, superfamily consists of the highly conserved seven-transmembrane
domain G-protein coupled receptors. These receptors are seemingly omnipresent in a
diversity of disease states, and are so adaptable that they can detect ligands as big and
complex as peptide hormones or as small and subtle as photons of light.
Binding of an agonist or antagonist by a receptor is the first step in a long cascade of
events leading to the ultimate, macroscopic physiological effect of the drug or endoge-
nous substance. In the case of receptors that operate on ion channels (see section 8.1),
the recognition site and the ion channel are part of the same supramolecular receptor
oligomer, and the ion channel will operate in direct response to ligand binding on dif-
ferent parts of the recognition subunits. A more complex chain of events takes place
in the vast majority of receptors—those utilizing chemical signaling, such as the
G-protein coupled receptors, for transmembrane chemical signaling.
The general scheme of transmembrane chemical signaling begins with the arrival of
an extracellular first messenger—a neurotransmitter, hormone, or another endogenous
substance, or an exogenous ligand such as a drug or bacterial toxin. The receptor–
ligand interaction takes place outside the cell, and in most instances the ligand does not
enter the cytoplasm. There are, however, some exceptions, as discussed in the previous
section on receptor internalization. Generally, the signal delivered by the ligand is con-
veyed to the cell interior by the receptor–ligand complex, which interacts with a trans-
ducer.The receptor–ligand–transducer ternary complex then interacts with an amplifier,
usually an enzyme, which produces a substance that activates an internal effector
(usually a phosphorylase kinase); the effector kinase then phosphorylates—and thereby
activates or deactivates—a site-specific enzyme that regulates the final cellular
response. Three systems, using different second messenger transducers, are known:
- The adenylate cyclase system
- The guanylate cyclase system
- The inositol triphosphate–diacylglycerol system
2.10.1 The Adenylate Cyclase SystemThis system has been elucidated by a number of investigators over a relatively long
period. Sutherland and Rall discovered cAMP in 1958, Rodbell and co-workers showed
the need for GTP in the process in 1971, and the complete sequence of events was
RECEPTORS: STRUCTURE AND PROPERTIES 93