RECEPTOR FEATURES

What do we have in a classical receptor?

It is membrane bound, and will have the ability to bind specific agonists because of its shape. Or, antagonists can bind which will prevent the agonist from binding. Also, we can have allosteric effectors—so that means that drugs or other pharmacological agents can bind at a place separate from the true agonist binding site but can either activate or antagonize the effect of the effector.

Then, most important, we must have a mechanism by which the binding of the agonist can be translated into a pharmacological effect… how is this pharmacological effect produced? In some cases, for instance with an acetylcholine receptor there is a channel within the large protein (there are 5 subunits making up the protein, stabilized by glycosylation) there is a water channel that goes through the membrane, when acetylcholine binds, the channel opens up and allows ions to go through so that the electrical effect transmission is elicited and you have the pharmacological effect.

In other cases, you have channels without real receptors, like Na channels . These are the kinds of channels involved with local anesthetics, they are sensitive to toxins.

Then you have other receptors like glutamate receptors in the CNS involved in psychedelic drugs such as ecstasy. Glutamate is the endogenous substance, but ecstacy is the exogenous substance. So it can exert transformation on the protein so that magnesium is released from the channel and opens the door for Na and Ca to come in and K to leave so that the channel is activated. At the same time, you have both endogenous and synthetic psychedelic drugs that are allosteric inhibitors and antagonize the opening to have a more relaxing effect… either you open or close the channel if you want to be excited or relaxed.

How do the receptors without channels work?

Protein receptors are bound to G-protein complexes, which exchanges GDP with GTP and makes them move to either activate or inhibit some kind of enzyme (like adenylate cyclase, or lipase or some kind of other enzyme) which will produce cAMP or cIMP other things to have some effect on other enzymes here and perhaps changing the Ca homeostasis of the cell, or something that is specific.

How do you get the specificity?

Can be obtained in different ways—what the receptors are willing to bind, where they are located, which enzymes are regulated by the cAMP that is released… which enzymes are available to be regulated.

Category: Pharmacology Notes