Specific Physiological Information Is Inherent in the Receptor/Ligand Complex, Not in the Hormone/ Neurotransmitter Molecule
Before discussing specific receptors, it is useful to elaborate on some important points about the nature and regulation of the information transfer between the external signal molecule and receptor.
This text provides ample evidence that the same hormone and especially the same neurotransmitter molecule can bind to different receptors. These different receptor-binding events send different information to the cell from the same external signal molecule. For example, acetylcholine is bound by two different receptors, the nicotinic ion channel described earlier and the muscarinic receptor, which is not an ion channel and sends completely different information to the cell. The hormone/neurotransmitter itself does not contain any specific information; rather, it is a simple signal, such as a phone ringing. One must answer the phone to receive the information. The information content of the hormone/neurotransmitter is really contained in the three- dimensional shape of the receptor molecule. The change in the shape of the receptor on binding the hormone/ neurotransmitter is the specific message to the cell.Cells can make themselves more or less sensitive to the signal of the hormone/neurotransmitter. For example, most cells respond to a prolonged period of exposure to hormone/ neurotransmitter by reducing their sensitivity to that molecule. For membrane receptors, one way is to internalize the receptors by endocytosis, fuse the endosome with a lysosome, and digest the receptor. Typically, membrane receptor number is decreased by endocytosis in response to a sustained high concentration of ligand. This is called downregulation of the receptor. This process allows the cell to adapt to high ligand concentrations. Receptor-Iigand interaction is a true chemical equilibrium, so the proportion of receptor-ligand complexes, which determines physiological response, depends on the concentration of both receptors and ligands. In the presence of a high ligand concentration, a decrease in receptor number returns the binding equilibrium to the normal proportion of bouπd∕unbound receptors. This allows the cell to respond to increases and decreases in ligand, even at high concentrations of ligand. Another way of regulating the response to a hormone/ neurotransmitter is to alter the binding function of the receptor, e.g., by phosphorylating it, so that its affinity for the ligand is reduced (desensitization) or increased (hypersensitization). Nuclear receptors appear to be less subject to short-term regulation of responsiveness, but at least some nuclear receptors require constant turnover by proteolytic breakdown and new synthesis in order to function.