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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by Janelle on March 25, 2002, at 20:55:33
Okay, let me run this by you geniuses ... it's about SSRI's.
Don't laugh, but there was a time when I thought there was only ONE serotonin reuptake pump in each and every person's brain, and that ALL SSRI's acted on that one pump. As a result, I figured that the various brands of SSRI's (e.g., Prozac, Zoloft, Paxil et al) were just marketing competition. HOWEVER, I could not understand why if each of these meds reached the one and only (same) serotonin reuptake pump in everyone's brain, why some people responded to Prozac, while others to Zoloft and still others to Paxil, and so on.
I've come a ways since that time and it has been my understanding that there are MANY serotonin reuptake pumps in the brain, and that each of these SSRI's may act on DIFFERENT pumps, and this is why an SSRI (e.g. Prozac) that works for Person A won't necessarily work on Person B.
Could it be that the reuptake pump that Prozac reaches might not be the reuptake pump that needs action in Person B? And that let's say Zoloft reaches the reuptake pump that needs action in Person B?
Do I have this right? If so, lemme know. If not, please correct me - in simple layman's English, please!
Posted by IsoM on March 26, 2002, at 0:08:44
In reply to BY GEORGE, have I got it??!!??, posted by Janelle on March 25, 2002, at 20:55:33
To be honest, I still have no clue why one SSRI will work for one but not another. I'm not even sure the neuropharmacologists know either. Maybe there's a Nobel prize in the works for you.
Posted by Janelle on March 26, 2002, at 0:54:35
In reply to Got Me??!! » Janelle, posted by IsoM on March 26, 2002, at 0:08:44
Is there more than one serotonin reputake pump in the human brain?
Posted by IsoM on March 26, 2002, at 4:19:21
In reply to ISO: can you verify this at least: » IsoM, posted by Janelle on March 26, 2002, at 0:54:35
In every cell in the body, there's innumerable pumps that transfer matter between the inside of a cell & the fluid outside the cell. All a pump is, is a special opening in the cell membrane that will only admit certain things through.
In the case of a serotonin reuptake pump, it's a small opening at the end of the neuron (the end that sends the neurotransmitters out). Think of it as your mouth - it's not always open. It only opens to take back the extra neurotransmitter molecules that weren't used by the receptor end & aren't doing anything - no waste. Okay so far?
Now the mind-boggling part - each of the billions of neurons in your brain has more than one sending end (the end that sends out neurotransmitters) & each of those ends have many reuptake pumps, serotonin included. Which means there's many, many billions of serotonin reuptake pumps in the brain.
So, yes, there's more than one in the brain. It's fascinating to learn, isn't it? That why I'm such a knowledge junkie.
Posted by BarbaraCat on March 26, 2002, at 12:10:52
In reply to Re: Pumps » Janelle, posted by IsoM on March 26, 2002, at 4:19:21
Janelle,
A very good book that explains much of this is "Molecules of Emotion" by Candace Pert. She is the researcher who discovered endorphins, the body's own opioid receptors. It's very interesting and enlightening and goes into great detail about receptors, ligands, reuptake pumps, etc. You should be able to order it from
www.amazon.com. - Barbara
Posted by Janelle on March 26, 2002, at 14:30:04
In reply to Pumps, etc. » IsoM, posted by BarbaraCat on March 26, 2002, at 12:10:52
Thanks for confirming that there ARE many, many serotonin reuptake pumps in the brain ... so now am I right that the different *brands* of SSRI's (e.g. Prozac, Zoloft, Paxil, Celexa, etc.) target DIFFERENT pumps?
And this could be why one of the SSRI's, let's say Prozac, will benefit Person A but not Person B because Person A needs the pumps affected by Prozac, whereas Person B needs the pumps that are affected by one of the other SSRI's? I hope I'm making this clear?!
Posted by BarbaraCat on March 26, 2002, at 16:38:38
In reply to SO, AM I RIGHT?!!??, posted by Janelle on March 26, 2002, at 14:30:04
Janelle,
Rather than there being many 'pumps', think many 'receptors'. There are few pumps, but many different receptors. Each transport pump can recycle many neurotransmitter molecules. Pumps are little workhorses and take care of a whole lot of transmitters and are not really choosy about which ones they're transporting, just as long as they get deposited back to the shores of the axon end. Kind of like the synaptic gap is an ocean between two shores and the reuptake pump is a ferry boat that can transport many people from the middle of the ocean back to the starting shore.An electrical spike fires down the long arm (axon), the 'sending' end of a neuron and releases the many different kinds of neurotransmitters into the synaptic cleft. Neurotransmitters are sent across this gap and received into their respective receptors on the membrame of another neuron. Receptors are large protein molecules that are embedded in the membrane of the receiving end of a neuron. The receptors fill up, change shape, an action potential is created causing an electrical spike to be sent down the axonal arm - to be repeated on and on. Whatever transmitters weren't used can get destroyed by other enzymes, so the reuptake pump removes them from the gap and deposits them into a safe holding area - the vesicles - which are sacks within the terminal end of the axon.
A neurotransmitter can occupy several different subtypes of receptors. Serotonin has at least 5 different kinds of receptor subtypes, dopamine at least 5, etc. To complicate matters further, each neuron has many terminating branches of an axon that look like a tree, each with it's own synapse, etc.
Some SSRI's target specific receptors which is why it's so tricky to get the right drug the first time. So many variables. BUT it's not only reuptake pumps that are implicated in SSRI's .
Recent research states that AD's work primarily by decreasing the number of the targeted receptors making the available neurotransmitters more efficient. And neurotransmittors are only the beginning - they're known as the 'first messenger system' in that they activiate something called a G-protein which is one of the components of DNA (guanine). G-protein then activates the second messenger system and this system is probably the most important one of all in that it regulates the DNA expression of genes, the structure of the cells, and the synthesis of transmittors in the first place - the underpinnings of the whole thing. Whew! What a work is man! - BCat
> Thanks for confirming that there ARE many, many serotonin reuptake pumps in the brain ... so now am I right that the different *brands* of SSRI's (e.g. Prozac, Zoloft, Paxil, Celexa, etc.) target DIFFERENT pumps?
>
> And this could be why one of the SSRI's, let's say Prozac, will benefit Person A but not Person B because Person A needs the pumps affected by Prozac, whereas Person B needs the pumps that are affected by one of the other SSRI's? I hope I'm making this clear?!
Posted by Mr.Scott on March 26, 2002, at 22:18:31
In reply to BY GEORGE, have I got it??!!??, posted by Janelle on March 25, 2002, at 20:55:33
Every serotonergic synapse in the brain has a serotonin reuptake pump. Each of these clean drugs affect a lot more than that though even though they are called clean drugs, they aren't. Each having different affects at different receptors and a whole chain of consequences both inside the cell and along the neuronal pathways and the pathways that those pathways are connected to and so on.
Try this link
http://www.preskorn.com/columns/0005.htmlScott
Posted by Janelle on March 27, 2002, at 1:14:26
In reply to Receptors not Pumps - and G-Proteins! » Janelle, posted by BarbaraCat on March 26, 2002, at 16:38:38
Barbara,
Eee-gads. Most of what you took the time and effort to post here went sailing over my head, but I'd like to review what I can get out of it with you and also ask a follow-up question or two!
Okay, I get that there are few pumps but many receptors. HOWEVER, you wrote "Pumps are little workhorses and take care of a whole lot of transmitters and are not really choosy about which ones they're transporting, just as long as they get deposited back to the shores of the axon end." Gee, I thought there were SPECIFIC pumps for SPECIFIC neurotransmitters, i.e. serotonin reuptake pumps, noradrenaline reuptake pumps, dopamine reuptake pumps, etc. You're saying no, that a pump will reuptake more than one kind of neurotransmitter?
You wrote: "The receptors fill up, change shape, an action potential is created causing an electrical spike to be sent down the axonal arm - to be repeated on and on." When you say "sent down the axonal arm," do you mean that the neuron that received the neurotransmitter is now sending it on the next neuron?
Can a neuron do both - it can receive and send?
Beyond this, I'm totally mystified! Wah ... I can't stand not being able to understand this stuff.
-frustrated Janelle
Posted by BarbaraCat on March 27, 2002, at 1:25:47
In reply to Re: BY GEORGE, have I got it??!!?? » Janelle, posted by Mr.Scott on March 26, 2002, at 22:18:31
Just want to clarify here. The two neurotransmitters most implicated in depression are serotonin and norepinephrine and there are different SEPARATE neuron types residing in different parts of the brain that 'specialize' in their respective neurotransmitters. There are a few reuptake pumps on the axonal terminal ends that recycle the serotonin, norepinephrine, dopamine, or whatever transmitter that neuron specializes in. However, there is not a separate pump for each neurotransmitter that is floating in the synaptic cleft. Things would get very crowded in there. Each reuptake pump can recycle boatloads of the transmitters back into the axonal vesicles. I'm not sure if this was what Janelle was asking or not, but wanted to highlight the fact of separate neurons handling separate classes of neurotransmitters, each with far fewer pumps than neurotransmitter molecules. - BCat
>
> Every serotonergic synapse in the brain has a serotonin reuptake pump. Each of these clean drugs affect a lot more than that though even though they are called clean drugs, they aren't. Each having different affects at different receptors and a whole chain of consequences both inside the cell and along the neuronal pathways and the pathways that those pathways are connected to and so on.
>
> Try this link
> http://www.preskorn.com/columns/0005.html
>
> Scott
Posted by Janelle on March 27, 2002, at 1:32:26
In reply to Re: BY GEORGE, have I got it??!!?? » Mr.Scott, posted by BarbaraCat on March 27, 2002, at 1:25:47
Posted by Janelle on March 27, 2002, at 1:39:06
In reply to Thanks BCAT, I finally get it! (nm) » BarbaraCat, posted by Janelle on March 27, 2002, at 1:32:26
BCat says there are only a few reuptake pumps, while Iso says there are MANY. EEEEEEEEEEEEEK, what's Janelle supposed to believe? (does Janelle even care anymore?!!)
Posted by BarbaraCat on March 27, 2002, at 1:57:03
In reply to BCat: HUH??!!?? » BarbaraCat, posted by Janelle on March 27, 2002, at 1:14:26
Janelle,
Sorry if I confused you. Yes, you are right about the pumps being dedicated to specific transmitters (each neuron is in fact dedicated to a separate transmitter). I had a bit of a brain fart there and wanted to say 'and the various other chemicals, or neurotransmitter-like molecules' also get recycled, but I'm not 100% sure of that. In other words, there are many drugs that mimic the shape of the actual neurochemicals, bind to the receptor and fools the receptor into thinking it's got the real thing. I just don't know if those other chemicals get recycled along with the real ones or not.To answer your question about whether neurons both receive and send, yes, absolutely. That's how neurons, and the entire brain (and stomache, BTW) communicate with each other. The neuron has a cell body, and then has many branches on the receiving end called dendrites, where the receptors are found. The neuron communicates with a web of other neurons by sending an electrical spike down a long arm called the axon. This long arm then branches and each branch terminates in the sending end, or the axonal terminal bulb. This is where the reuptake pumps are found and the neurotransmitters are both stored and released. Each axonal terminal connects (across the synaptic cleft) with the dendrite of another neuron. And recall that each neuron has many many dendrites and axon terminal bulbs like the branches of a tree. Each neuron is communicating with God knows how many other neurons, but it's alot.
The brain is highly electrical. The only way that electric impulses can communicate once they reach that synaptic cleft is by chemical means, hence the neurotransmitters. They get released, float across the synaptic cleft and hopefully find a receptor. Once the neurotransmitters lock into the receptors of ANOTHER neuron's dendrites, an electrical spike is initiated, sending the impulse down the axon to the axonal terminal bulbs and on and on. It's pretty amazing stuff and to think of all that activity, coordination, opening and closing of gates, is mind boggling. It's a wonder that more doesn't go wrong with our wiring. - BCat
Posted by BarbaraCat on March 27, 2002, at 2:01:19
In reply to BCat + ISO: your info here conflicts!, posted by Janelle on March 27, 2002, at 1:39:06
There may be many pumps, but certainly not one pump for each neurotransmitter molecule. That would be a huge waste of real estate. Each pump can recycle many neurotranmitters. All it has to do is shunt the neurotransmitter molecules into an axonal vesicle, one after another, like a conveyer belt.
Posted by Janelle on March 27, 2002, at 2:24:44
In reply to Re: BCat + ISO: your info here conflicts! » Janelle, posted by BarbaraCat on March 27, 2002, at 2:01:19
I followed most of your most recent explanation. I just have one OT (Off Topic) question - what on earth is your educational background? Did you go to college and if so what did you study -- do you have science, biology, anatomy in your background? I am in absolute AWE of all that info you rattled off to me in this thread!
Posted by BarbaraCat on March 27, 2002, at 14:09:38
In reply to BCat: wow, I followed most of that: » BarbaraCat, posted by Janelle on March 27, 2002, at 2:24:44
Thanks, Janelle. It was alot of fun to dig deep into my own neurons and books to spew it forth. I don't have a science background per se (I was in computers when I was working) but I've taken alot of science college classes cause I was interested. Biology and Chemistry classes were very helpful (and necessary if you want to get down to the nitty gritty of the subject), but the most informative info I got was from two semesters of a college class I took about 10 years ago called 'Biological Psychology'. It went into the details of brain structures and mechanics and neurochemistry (I'm glad I had the biology and chem previously - they were invaluable). It was absolutely fascinating and filled me with incredible awe and appreciation for the miracle of how our brain works.
From there I just soaked up whatever I could about the subject, reading books, articles, whatever, because the subject is close to home. I have a passionate interest in the subject because it's so amazing, but also because I want to understand what's going on with my own illness. Also, I think it's VERY important for anyone getting healthcare for their mood disorders become informed. I see my pdoc once a month if I'm lucky and I'm usually the one suggesting meds for me. If I left it up to managed care, I'd be in the hands of well meaning but overworked people who don't have time to think about my condition.
There are so many really good books out there that are good reads and very understandable. Also, this forum is probably the best resource available. I've learned so much from the Babblers. - BCat
This is the end of the thread.
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