transported to the interior of the cell. Perhaps the most important role of internalization
is the removal of receptors from the plasma membrane, the down-regulation of a receptor
population.
2.9 RECEPTOR TYPES AS DETERMINED BY
MOLECULAR MODE OF ACTION
The goal of a drug molecule is to influence cellular function via a receptor-mediated
mechanism. Cellular function may be conceptualized into three very broad categories
of activity:
- Transmitting information from one cell to an adjacent cell (via voltage-gated and
ligand-gated ion channels). - Transmitting information from the exterior of the cell to the interior of the cell (via
G-protein coupled receptors). - Biosynthetic activity within the interior of the cell (in the nucleus and cytosol via
enzyme-catalyzed activities).
Accordingly, receptor types may be categorized into five types, which address these
broad categories of cellular function:
- Voltage-gated ion channels
- Ligand-gated ion channels
- G-protein coupled receptors
- Enzymes and ligand-operated enzymes
- Protein synthesis-regulating receptors
Voltage-gated ion channels (Na+,Ca^2 +, and K+ion channels) are large transmembrane
proteins whose conformation is dependent upon the transmembrane voltage gradient.
By controlling transmembrane transport of ions they control electrical activity (e.g., the
neuronal action potential) and thus the transmission of information from cell to cell.
Ligand-gated ion channels are large transmembrane proteins whose conformation is
dependent upon the presence or absence of particular ligands bound to the protein;
ligand binding causes the channel to open and ions to cross the cellular membrane,
thereby influencing cellular function. The acetylcholine, GABA-A, NMDA, and glycine
receptors are ligand-gated ion channels. G proteins (discussed in detail in the next
section) are proteins that permit a ligand binding to the exterior of the cell to influence
metabolic processes, such as enzymatic activity, within the cell. Since enzymes are
catalysts that promote biosynthesis within the cell, they are logical receptors for drug
action. Finally, protein synthesis-regulating receptors are found in both the cytosol and
the nucleus and are capable of binding steroid and thyroid hormones. The hormone
binds to a domain on the receptor protein, which in turn binds to a particular nucleotide
sequence on a gene, thereby regulating its transcription.
This list of potential receptors encompasses the majority of receptors that permit
drug regulation of endogenous biochemical processes. However, this list of receptors is
not comprehensive for all drugs available for the treatment of human disease. Infections
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