Receptors as Drug Targets

Receptors: Membrane-Embedded Signal Proteins

Receptors are proteins that form the core of the body's chemical communication system. Most receptor proteins sit embedded within the cell membrane, with only a small extracellular portion - carrying the receptor's active or binding site - projecting outward into the space surrounding the cell (see the cutaway cell-membrane diagram in Figure 16.4, whose cover art shows a receptor protein threaded through the phospholipid bilayer with its binding site opening onto the outer surface).

Mechanism of signal transfer. Chemical messenger molecules (such as neurotransmitters and hormones) carry signals between neurons, and between neurons and muscle cells, by binding at this externally exposed binding site. The binding event itself changes the physical shape of the receptor - an induced-fit process - and it is this shape change, propagated through to the receptor's intracellular end, that transmits the message into the interior of the cell. Crucially, the messenger molecule itself never has to enter the cell; only the shape-change signal does. Figure 16.5's three-panel cover art traces this full sequence - the messenger approaching, the induced-fit shape change with the message radiating inward, and the receptor reverting to its resting shape once the messenger detaches.

Selectivity. Different receptor proteins respond to different chemical messengers because their binding sites differ from one another in shape, internal geometry and amino-acid composition, so only a messenger of complementary shape and chemistry will dock efficiently.

Drugs that act on receptors fall into two functional categories: …