Posted by Shawn. T. on July 25, 2002, at 18:40:39
In reply to Re: downregulation??, posted by cybercafe on July 24, 2002, at 21:56:31
I believe it is a combination of two molecules which can fit another molecule into it.
Here's a picture:
http://www.chem.sci.osaka-u.ac.jp/lab/nakasuji/qqh.html
Here's some interesting info about mad cow disease involving dimers:
http://www.lerner.ccf.org/news/20010926.phpOK the following may or may not be a good example of how dimers affect neuronal processes, but I think it should clue you in on what is generally happening. My belief is that certain hormones can lock into dimers which are located in G-proteins, and this may cause certain pairs of receptors to manipulate their coupling function. I believe that the coupling function is often manipulation of calcium or potassium channels. Lets consider a certain action of estrogen for example. If estrogen attaches into a dimer linked to a mu opioid receptor and a GABAb receptor, the two receptors decrease their functional coupling to an inward rectifying K+ channel. Rectifying would seem to be used in the electrical context here, so I believe it means to convert alternating current into direct current.
So estrogen causes a cell to become less positive than its surroundings. So it would inhibit an action potential, therefore making neurotransmitter release less likely (the neuron is resistant to weak stimuli). Note that GABAb receptors can also inhibit N type voltage operated calcium channels. Mu opioid receptors can inhibit various other types of calcium channels which may be types N, P, and Q (and they may also possibly activate L type calcium channels). The two receptors share the ability to activate k+ channels. If the neuron that I am describing is on your finger tip, I think that the effect of estrogen on it would be somewhat numbing.
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=23673622There was a thread earlier about GHB; I'll try to apply what I've said to it. There have been arguments made that GHB may actually be a neurotransmitter, but I don't agree. I believe that it probably serves a role similar to estrogen as described above, but it is not as widely utilized as estrogen. I believe that it interacts with both presynaptic and postsynaptic GABAb receptors. GHB increases dopamine release, and I believe that it may accomplish this via G proteins. It may fit into the dimer (tetramer?) connected to both GABAb and dopamine receptor D2 (the presynaptic autoreceptor). This would effectively reverse the action of the GABA receptor and allow the release of dopamine. It's postsynaptic effects are probably responsible for sedation. Opioids and THC can accomplish the same process in the ventral tegmental area. Note how all three substances can relieve pain, cause euphoria, and put you to sleep.
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=24177273
The difference between GABAa receptors and GABAb receptors seems to be that the a receptors are linked to Cl- channels, and the b receptors are linked to K+ channels. I would suggest that a GABAb agonist like Baclofen may be the successor to the benzodiazepines. It has been shown to be very useful in withdrawal from opiates and other substances. It would be similar to using clonodine for such a purpose, but would lack the negative mental effects. Clonidine is an alpha-2-adrenergic agonist, and I believe that alpha-2-adrenergic receptors are linked via G protein to postsynaptic dopamine D2 receptors, which decrease adenylyl cyclase levels. One school of opiate withdrawal thought points to a rebound increase in adenylyl cyclase to be the cause of withdrawal.http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=29859723
What I am doing right now is trying to figure some of the combinations that the monoamines can make with other receptors. The thing that I find interesting is how many of them are involved in pain regulation. For instance, 5-HT3 may be negatively coupled with GABAb. GABAb may be able to inhibit substance P release. So when 5-HT3 is activated, substance P is released. A 5-HT3 antagonist like Remeron should therefore inhibit substance P release, which it has been shown to do. Extrapolating data is very useful in my opinion. I can really cover some ground in figuring out side effects based on this new methodology.
http://nootropics.com/5-ht3/index.html
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> hey Shawn, what is a dimer? dictionary.com tells me it is a molecule made up of two identical molecules, but i'm thinking X + X = X --> X = 0
poster:Shawn. T.
thread:113408
URL: http://www.dr-bob.org/babble/20020725/msgs/113720.html