|MadSci Network: Biochemistry|
Hello Heather, You raise an interesting question. Drugs that interfere directly with the binding of a neurotransmitter (NT) to a receptor are called antagonists and they can compete for the binding site. However, a lot of other modulating factors can also affect the affinity of the receptor for any given NT. Certain drugs can bind at sites other the ligand binding site and cause allosteric changes in the conformation of the receptor which in turn can alter the affinity of the ligand binding site. A good example of this occurs at the NMDA-sensitive class of glutamate receptors. Glutamate binds at the ligand binding site and causes the NMDA receptor to open an intrinsic cation channel which is also part of its structure. Glycine, another neurotransmitter with it's own receptor, can also bind the NMDA receptor, but not at the binding site and can potentiate the effects of glutamate by an allosteric mechanism. For another class of receptors which by the NT GABA, drugs such as benzodiazepines have similar effects. Also, one must keep in mind that all of these receptors are transmembrane proteins which means they have surfaces exposed to the outside and the inside of the cell. Those areas exposed to the inside (so-called cytoplasmic domains) are sensitive to modulation by protein kinases (which can phosphorylate the receptor), phosphatases (which have the opposite effects) and a host of other cellular proteins. Modulation of the cytoplasmic domains can have dramatic effects on the extracellular binding site thus reducing or increasing the affinity for the NT. So you see, it's not just the binding site itself that determines the affinity for the ligand but rather the global state of the receptor. Hope this helps, Terry
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