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.
>
> -------------------------------------------------------
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> Very.
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> 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.
poster:Cam W.
thread:19944
URL: http://www.dr-bob.org/babble/20000128/msgs/20127.html