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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Sam on January 28, 2000, at 21:29:53
Do volkswagons work as well as toyotas?
Posted by Cam W. on January 29, 2000, at 10:08:20
In reply to What is an autoreceptor?, posted by Sam on January 28, 2000, at 21:29:53
> Do volkswagons work as well as toyotas?
Sam - Don't buy foreign, stick with the North American made models.
Autoreceptors are located on the nerve cell body and at the end of the nerve cell axon. They turn off the flow of neurotransmitter out of a cell via a biofeedback mechanism. When a neurotransmitter (NT) is released from a cell, some of that NT binds to the autoreceptor (located on the presynaptic side of the synaptic cleft or gap) and shuts off the flow of the NT out of the nerve cell. By blocking the autoreceptor you are essentially "shutting off" the off button and more NT is released into the synaptic gap, hopefully increasing neurotransmission. Hope that this is clear. - Cam W.
Posted by Sam on January 29, 2000, at 16:22:55
In reply to Re: What is an autoreceptor?, posted by Cam W. on January 29, 2000, at 10:08:20
Is this the same as reuptake?
Posted by Cam W. on January 29, 2000, at 22:16:08
In reply to Re: What is an autoreceptor?, posted by Sam on January 29, 2000, at 16:22:55
> Is this the same as reuptake?
Sam - No an autoreceptor is different from a reuptake transporter. The autoreceptor increase the neurotransmitter (NT) in the synaptic cleft by turning off the feedback mechanism that turns off the release of NT from the nerve cell.
A reuptake transporter is a conservation mechanism that the body has so it doesn't have to keep making more NT all of the time. After the NT is released into the synaptic cleft from the nerve cell and binds to the receptors on the adjacent nerve cell (carrying the electrical signal across the synaptic cleft) the NT releases from the receptor and the reuptake transporter draws a portion of the NT back into the nerve cell it was released from. The rest of the NT (if it is a monoamine) is metabolized by monoamine oxidase (MAO). In this way the body does not have to make as much NT as it reuses the NT that is taken up back into the cell by the transporter.
In depression, we know that some NTs are in lower quantities than is seen in non-depressed people. Serotonin is observed to be lower so the SSRIs (selective serotonin reuptake inhibitors) block the nerve cell from taking up the serotonin back into the cell. In essence, this is raising the amount of serotonin in the synaptic cleft (which has lower amounts present in a depressed person) and forces the body to begin to produce more serotonin, thus it is thought that this is one way (of possibly many more) that SSRIs relieve the symptoms of depression. I know this is quite detailed & I hope it is clear. _ Cam W.
Posted by Sam on January 29, 2000, at 23:12:16
In reply to Re: What is an autoreceptor?, posted by Cam W. on January 29, 2000, at 22:16:08
Blocking or antagonizing either the autoreceptor or the reuptake site would have the same effect then. One would interfer with a negative feedback control mechanism and the other would block the active transport out of the synaptic cleft. Both increasing concentrations in the synaptic cleft.
Posted by Cam W. on January 29, 2000, at 23:21:19
In reply to Re: What is an autoreceptor?, posted by Sam on January 29, 2000, at 23:12:16
> Blocking or antagonizing either the autoreceptor or the reuptake site would have the same effect then. One would interfer with a negative feedback control mechanism and the other would block the active transport out of the synaptic cleft. Both increasing concentrations in the synaptic cleft.
Sam - Exactly! But to confuse you further, although the increase of serotonin (&/or norepinephrine) may be a part of the relief of depression, this may only be a small part, or even just artifact. The signal across the cleft is improved, but antidepressant effects on glucocorticoids or the HPA axis (hypothalamus-pituitary-arenal) may be more important for a sustained antidepressant effect. This may explain why SSRIs and Wellbutrin, with seemingly opposite effects, both improve the symptoms of depression. These are fairly new theories (within the last couple of years) but they are intriguing. Hope this helps. - Cam W.
Posted by Elizabeth on January 30, 2000, at 8:53:40
In reply to What is an autoreceptor?, posted by Sam on January 28, 2000, at 21:29:53
It's just a receptor whose ligand is fired by the cell it's on. e.g., a serotonergic receptor that is on a serotonin-firing neuron would be a serotonergic autoreceptor.
> Do volkswagons work as well as toyotas?
I dunno, but those new bugs are awful cute.
Posted by Cam W. on January 30, 2000, at 10:37:01
In reply to Re: What is an autoreceptor?, posted by Elizabeth on January 30, 2000, at 8:53:40
> It's just a receptor whose ligand is fired by the cell it's on. e.g., a serotonergic receptor that is on a serotonin-firing neuron would be a serotonergic autoreceptor.
>
> > Do volkswagons work as well as toyotas?
>
> I dunno, but those new bugs are awful cute.Elizabeth - I like it when someone can say what I try to, in a sentence. A NT that binds to the same cell as it is released from, cool. Just a further note; the reuptake transporter is also located on the presynaptic membrane of the synaptic cleft.
- Cam W. (still support the North American economy & buy locally made cars)
Posted by Ruth on January 30, 2000, at 12:20:10
In reply to Re: What is an autoreceptor?, posted by Cam W. on January 29, 2000, at 23:21:19
Your explanations are very clear and very helpful to me in understanding something that I just haven't "gotten" previously. Thanks.
> > Blocking or antagonizing either the autoreceptor or the reuptake site would have the same effect then. One would interfer with a negative feedback control mechanism and the other would block the active transport out of the synaptic cleft. Both increasing concentrations in the synaptic cleft.
>
> Sam - Exactly! But to confuse you further, although the increase of serotonin (&/or norepinephrine) may be a part of the relief of depression, this may only be a small part, or even just artifact. The signal across the cleft is improved, but antidepressant effects on glucocorticoids or the HPA axis (hypothalamus-pituitary-arenal) may be more important for a sustained antidepressant effect. This may explain why SSRIs and Wellbutrin, with seemingly opposite effects, both improve the symptoms of depression. These are fairly new theories (within the last couple of years) but they are intriguing. Hope this helps. - Cam W.
Posted by Scott L. Schofield on January 30, 2000, at 12:39:27
In reply to Re: What is an autoreceptor?, posted by Cam W. on January 29, 2000, at 10:08:20
> Autoreceptors are located on the nerve cell body and at the end of the nerve cell axon. They turn off the flow of neurotransmitter out of a cell via a biofeedback mechanism. When a neurotransmitter (NT) is released from a cell, some of that NT binds to the autoreceptor (located on the presynaptic side of the synaptic cleft or gap) and shuts off the flow of the NT out of the nerve cell. By blocking the autoreceptor you are essentially "shutting off" the off button and more NT is released into the synaptic gap, hopefully increasing neurotransmission. Hope that this is clear. - Cam W.
-------------------------------------------------------
Very.
Hi Cam W.
I have more questions that I'm too lazy to research:
1. Do autoreceptors also help control the neurotransmitter factories?
2. Are there post-synaptic autoreceptors that help inhibit the nerve from "over-doing" it?
3. If so, how might buspirone and pindolol be involved in serotergic neurotransmission?
This is pretty cool. Now I don't even have to go to Medline.
- Scott
Posted by Cam W. on January 30, 2000, at 17:58:18
In reply to Re: What is an autoreceptor? - I want more., posted by Scott L. Schofield on January 30, 2000, at 12:39:27
> > Autoreceptors are located on the nerve cell body and at the end of the nerve cell axon. They turn off the flow of neurotransmitter out of a cell via a biofeedback mechanism. When a neurotransmitter (NT) is released from a cell, some of that NT binds to the autoreceptor (located on the presynaptic side of the synaptic cleft or gap) and shuts off the flow of the NT out of the nerve cell. By blocking the autoreceptor you are essentially "shutting off" the off button and more NT is released into the synaptic gap, hopefully increasing neurotransmission. Hope that this is clear. - Cam W.
>
> -------------------------------------------------------
>
> Very.
>
> Hi Cam W.
>
> I have more questions that I'm too lazy to research:
>
> 1. Do autoreceptors also help control the neurotransmitter factories?
>
> 2. Are there post-synaptic autoreceptors that help inhibit the nerve from "over-doing" it?
>
> 3. If so, how might buspirone and pindolol be involved in serotergic neurotransmission?
>
>
> This is pretty cool. Now I don't even have to go to Medline.
>
>
> - ScottScott - I will try to answer you question to the best of my present ability.
1. By stopping the production of the NT, I would assume that the autoreceptors "influence" the production of NTs. (I have no precise corroborating evidence - I have seen no precise studies on the mechanism of action here; probably secondary messengers are at work here. *Dr.BOB* - Have you heard anything on this.
2.As for post-synaptic serotonin receptors, they are known to be in an overabundance in depression. Presumably this up-regulation of these receptors is in response to decreased amount of serotonin being released from the presynaptic nerve cell. As you increase the amount of serotonin in the synaptic cleft (by the various factors that have been mentioned previously) these overabundance of post-synaptic receptors are down-regulated (or decreased) to "normal" levels. The signal across the synapse is then more normal. Interestingly, this down-regulation takes approximately 2-4 weeks to occur; the time it takes for an antidepressant to start to work. As a caveat, this is probably not the whole story on the mechanism(s) of action of antidepressants.
3.Pindolol, being an autoreceptor blocking agent, is thought to decrease the lag time between initiation of therapy and antidepressant response. While I have seen this in action, I cannot be sure that the placebo effect is not at work here. It works well in some people and not at all in others.
Buspirone, a drug that seems to work better in people who have never taken an benzodiazepine, presumably because it lacks the "fun" effects of the benzos - "I don't feel the grogginess or euphoria I feel with Valium" is what I hear). Buspirone also has a lag time of about 2 to 4 weeks to begin working. It is an agonist at the serotonin autoreceptor, so it prevents the release of serotonin by the presynaptic neuron. Also, buspirone has an affinity for dopamine-D2 receptors where it acts as a mixed agonist/antagonist. The clinically antianxiety mechanism(s) of action have not been elucidated (to my knowledge).Caveat - The following is an assumption on my part. Since buspirone blocks dopamine-D2 receptors, presumably decreasing dopamine neurotransmission, and dopamine keeps serotonin levels in check (and vice versa), serotonergic transmission should be increased. (Confounding factors - buspirone also stimulates dopamine-D2 receptors and enhances the feedback mechanism slowing serotonin release from the presynaptic nerve cell, you would expect an opposite effect. In essence, the answer to you question regarding buspirone is - I don't know. Maybe someone else out ther knows. (Can you help Dr. BOB?)
Lastly Scott, DO NOT take anything I say as gospel, I have been wrong before and I will be again. Please check my answers against Medline. Sincerely - Cam W.
This is the end of the thread.
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