Altering neurotransmission 2b: post-release

So we can see, then, that we can affect how much is released. But what we also have to think about is what happens if we do get normal release of neurotransmitter. So I’d like to remind you of what normally happens. What normally happens is that our transmitter molecule will find, and bind to, a receptor on the post-synaptic cell’s dendrite. And this will bring about some response in the post-synaptic cell. So how can we affect this process? Well, there’s a number of ways in which we can do that. We can, for example, have a situation where we have our drug agent binding here to the receptor.

And clearly what that does is to interfere with the normal ability of our usual transmitter to bind. We would call a drug like this an antagonist. But we can also get a different arrangement, whereby our drug can bind to the receptor and can cause a normal, or near normal, response in the post-synaptic cell. We’d call this kind of drug an agonist. If you’re a smoker, you’ll know that tobacco contains nicotine. And nicotine is an agonist at one of these receptors. And thus, the effects that nicotine brings about are coming about because of its action on these receptors.

If you’ve ever taken a drug because you’re experiencing some pain– an analgesic drug– mostly they work also by having an action on the receptor, which is independent of the real, natural neurotransmitter.

Now, what we haven’t really considered before is what happens once our neurotransmitter’s been released her into the synapse. Clearly, it’s going to need to be cleared away in some fashion. And essentially, there are two ways in which this can happen. One is that the molecules of transmitter may be taken back into the presynaptic terminal, essentially to be recycled back into vesicles. Now, what that means, of course, is that the concentration of neurotransmitter here in the synapse is, to some extent, dependent on how active these transporters are. So if we were to block the action of that transporter, you should be able to see that it follows that the level of our neurotransmitter, here in the synapse, should go up.

You may have heard of a drug called Prozac. Now, Prozac is used often for people who have clinical depression, and Prozac works in just this way. It blocks the transporter that is responsible for the re-uptake of a particular neurotransmitter called serotonin, or 5-HT. There is another potential fate for our released neurotransmitter, and that is that it will be metabolised, broken down, or degraded. And to do that, we utilise a variety of very specific enzymes. One of the enzymes for one of the transmitters says is something called cholinesterase. Now, cholinesterase breaks down the neurotransmitter, acetylcholine. If we use a drug that interferes with that cholinesterase, it won’t be as efficient at breaking down the acetylcholine.

So again, we will see a rise of the level of acetylcholine in our synapse. Now, this can be used for good and for bad. If you suffer from a disorder of a dysfunction in a particular type of synapse we find in your body, between the nervous system and this time, a muscle, you may experience muscle weakness. In this condition, where we want to maximise our stimulation of the post-synaptic receptors, we need to maximise our amount of acetylcholine here. And we do that by using one of these cholinesterase inhibitors, or anti-cholinesterases. Clearly, an action for the good. However, you may also be aware that there are nerve gases. Things that are used against people across the world, often in war situations.

These are very toxic for similar reasons. Many of them are anti-cholinesterases. They prevent the breakdown of acetylcholine. We get excessive activity here, in the post-synaptic cell, and this is what causes the toxic effects. So as you can see, when we’re thinking about drugs for therapeutic use, perhaps drugs that might be used, like amphetamine, perhaps drugs that are used for rather unpleasant purposes, we have a number of unusual and variable targets here, within the synapse.