Why are there different types of serotonin receptor, but only one type of serotonin?

[perpetualdawn]

Are there any explanations for this?

 

[chaos_destroy]

My guess would be that they have somewhat different signaling pathway bias and probably have different responses to other endogenous molecules which may act as modulators to serotonin. This would allow for different effects in different cells depending on which receptors are expressed.

 

[sekio]

Well, it's not just serotonin, there are also diverse types of receptors for other major neurotransmitters: GABA, acetylcholine, glutamate, dopamine, norepinephrine and adrenaline, etc.

As chaos_destroy points out, different receptors for serotonin can be modulated using various ligands, which makes sense if you want the serotonin to do different things in different parts of the organism. Depending on what other cellular machinery is 'attached' to the receptors (assuming they are G-protein coupled receptors aka GPCRs) different receptors can trigger different responses.

 

[serotonin2A]

The other posts above touched on some of the reasons why this is thought to occur, but it doesn't give the whole story.

Having more than one receptor allows the action of serotonin to be fine-tuned. First, you can get inhibitory or excitatory effects depending on the receptor subtype and the specific G proteins it couples to. Some receptors have higher affinity for serotonin and some have lower affinity, so low levels of serotonin activation may preferentially activate one receptor subtype, and higher levels may have more general effects. And the receptor effects can have different time courses. So serotonin may activate one receptor for a short period and it may simultaneously may act at another receptor for a longer period of time.

(I figured I would add in an example):
A classic example is 5-HT1A and 5-HT2A receptors on cortical pyramidal neurons. 5-HT2A produces a long-lasting facilitation of excitation, and 5-HT1A inhibits firing with a shorter time-course. So when serotonin is applied experimentally it tends to inhibit the neurons first and then produces a longer-lasting increase in excitability. This may help to confine pyramidal neuron activity within a specific window. And serotonin has higher affinity for 5-HT1A than for 5-HT2A, which means that it is more likely to have an inhibitory effect than an excitatory modulatory effect. That is probably a good thing because it would tend to restrain the excitatory response to serotonin.

 

[perpetualdawn]

Thank you for your answers, I've learned a lot here.

Well, it's not just serotonin, there are also diverse types of receptors for other major neurotransmitters: GABA, acetylcholine, glutamate, dopamine, norepinephrine and adrenaline, etc.

Figured as much, but thought I'd ask about serotonin as a case study.

A classic example is 5-HT1A and 5-HT2A receptors on cortical pyramidal neurons. 5-HT2A produces a long-lasting facilitation of excitation, and 5-HT1A inhibits firing with a shorter time-course. So when serotonin is applied experimentally it tends to inhibit the neurons first and then produces a longer-lasting increase in excitability. This may help to confine pyramidal neuron activity within a specific window. And serotonin has higher affinity for 5-HT1A than for 5-HT2A, which means that it is more likely to have an inhibitory effect than an excitatory modulatory effect. That is probably a good thing because it would tend to restrain the excitatory response to serotonin.

By "confine pyramidal neuron activity within a specific window" do you mean that the this is a mechanism by which the neuron is confined to fire within only a certain window of excitement? So if there's too little or too much serotonin excitement, it won't fire? Or is it more like a time window? Or both. Just want to check if I'm understanding this.

 

[serotonin2A]

Thank you for your answers, I've learned a lot here.



Figured as much, but thought I'd ask about serotonin as a case study.



By "confine pyramidal neuron activity within a specific window" do you mean that the this is a mechanism by which the neuron is confined to fire within only a certain window of excitement? So if there's too little or too much serotonin excitement, it won't fire? Or is it more like a time window? Or both. Just want to check if I'm understanding this.

I guess you could describe it as a frequency window, because this mechanism would potentially help to restrict the firing of the neuron to within a specific range of frequencies. It's not that the neuron wouldn't fire in the absence of serotonin, because it would. But 5-HT2A induces a few different effects (depolarization and alteration of ion channel conductances) that make the cells a little more likely to fire when an excitatory signal (e.g. glutamate) is present. On the other hand, 5-HT1A tends to be located in a part of the pyramidal cell that is more "downstream" from where 5-HT2A is localized. It is positioned to put the "brakes" on firing. So 5-HT2A would tend to keep the cell firing at least a certain level, and 5-HT1A would act to dampen the firing rate, so activity would be more likely to fall within that specific range.

This is, of course, an oversimplification of the actual story.

 

[embryo923]

I was going to make a thread about this but this seems like some people here may be able to answer some of my questions.

I took DXM almost daily for 7 years, in a world of pure bliss...wrote a lot of good songs, even got myself on tour with En Esch from KMFDM in his North American touring 2012 (youtube it), which was a huge commitment and task but I did it, while a heavy DXM addict.....so the DXM didn't debilitate me, it just made me MORE ambitious and creative and artsy. However I eventually quit because I was starting to get some serious chronic fatigue, and got into a car accident as a result of a DXM hangover.
So I went to a shrink, and since DXM increases serotonin, I was RX'd Zoloft, which is an SSRI. However I get nothing like the happy, excited feeling that DXM gave me on Zoloft. Almost the opposite..I mean Zoloft definitely help with my depression, as did DXM (which is why I took DXM in the first place, long story..)

So what is different about Zoloft that it doesn't' make me feel that psychedelic happy, creative feeling that DXM does? What is the neurological explaination and is there any way I can take a supplement or additional medication to make me feel that way? Because that is my most productive part of my life, artistically. And most socially successful. I'm a hermit now and I don't like it, but lack the motivation to go out. I just want to understand the difference between DXM and Zoloft in terms of affecting Serotonin.

I have also read about the combination of 5htP or SAM-e along with L-Tyrosine to improve the aspects of my neurological processes that I want to improve. Thank you for any input.

 

[serotonin2A]

The pharmacology of DXM is complex and there is no reason to conclude that the effects you experienced were exclusively mediated by interactions with SERT. NMDA receptors and sigma-1 sites are thought to play an important role in the antidepressant effects of DXM.

 

[DevilSolution]

Ill offer a quick analogy regarding the difference between ssri's and 5-htp 2b (non) selective agnosist.

Okay so imagine that the cities and towns in your country represent specific neurons of the brain each connected with railway lines and stations. An ssri help modulate the traffic of people per station of a particular type (serotonin) which for arguments sake is flamboyent people, therefor an ssri will help contain the amount of flamboyant people arriving at a particular location....

5ht2b agnonists (such as DXM) will metabolise lots of flamboyant people and send them to important stations which overloads the local area with said stereotype....

Regards...