cAMP system - Cyclic adenosine monophosphate | how to encourage it

[chugs]

With my very layman knowledge, and a boring day at work I was reading up on how opiates function in our brain.

I was lead to believe that the very same receptors that opiates bind to, the MU, are usually meant for Cyclic adenosine monophosphate.

My reading lead me to understand that consistent use of opiates results in a reduction in the production of Cyclic adenosine monophosphate and that when the opiates leave your brain, that with no Cyclic adenosine monophosphate you end up with a slight problem known as withdrawals.

So my question is there any known way to kick start the production of Cyclic adenosine monophosphate in your brain? Google wasn't very friendly re searching for this and I don't really know the key words to describe a drug therapy that causes such an outcome.

Any suggestions?

 

[footscrazy]

I would be interested to find out more about this.

cAMP is apparently synthesised from ATP. 'The energy used by human cells requires the hydrolysis of 100 to 150 moles of ATP daily, which is around 50 to 75 kg. A human will typically use up his or her body weight of ATP over the course of the day. This means that each ATP molecule is recycled 1000 to 1500 times during a single day (100 / 0.1 = 1000). ATP cannot be stored, hence its consumption closely follows its synthesis.'

Prob not relevent but I just thought that is insane! We go through 50-75 kilos of ATP everyday!

 

[Mr Blonde]

Opioid receptors are not 'normally reserved' for cyclic adenosine monophosphate. They are there for binding to by endorphins. cAMP is a chemical messenger, particularly involved in sending signals received from outside the cell to the inside of cell to result in the expected changes. Opioid receptors are G protein coupled receptors; once they have been bound to by an agonist the conformation of the receptor changes and this leads to further signalling inside the neurons and cells in questions. cAMP is definitely involved in this signalling, and it has been shown that addiction does alter the proper functioning of both the receptors (down-regulation) and the signalling mechanisms inside the cell. This is an interesting read if you have the time.

I would dare to say that most of the effects of opioid withdrawal are due to down-regulation of opioid receptors and hence the inability of endorphins to properly perform the roles they are expected to within the brain.

I don't think you will find an easy way to boost your cAMP levels, and to target those levels in the brain. cAMP is involved in many cellular process in the body, from neuronal signalling to the function of major organs and skeletal muscle.

footscrazy: That is an interesting fact there.

 

[footscrazy]

I've wondered about downregulation of opiod receptors causing withdrawals - does this mean that the pain experienced in opiate withdrawal is always with us - but our endorphins/opiod system, when functioning correctly, just 'know' that they need to dull that pain...? Or is the pain of withdrawal caused by another pathway as well? Does cutting your finger or any other injury hurt more in withdrawal...?

 

[opi8]

I've found that any pain is amplified when I'm in withdrawal.

 

[Neuroprotection]

Interesting questions, I will try to answer based on my own knowledge I gathered from reading along time ago.
first of all, opioid receptors, particularly the mu subtype are g protein coupled receptors, and many of their downstream affects, that is the affect inside the neuron, relies, on second messengers a key one being cyclic adenosine monophosphate or CAMP.
A well known affect of mu opioid receptors is to inhibit the enzyme adenilate cyclase, rapidly reducing intracellular CAMP levels. This is known to mediat many of the affects of opioid drugs like morphine. Some neurotransmitters like epinephrine and nor epinephrine, bind to receptors which function to increase CAMP levels, therefore sensitivity to these neurotransmitters is diminished in neurons targeted with strong mu opioid agonists.
However, during withdrawal, an exess of CAMP is produced due to overactivation of adenilate cyclase, resulting in supper sensitivity to adrenalin and hyperexitable neurons. Also, it must be noted that CAMP, is only one molecule involved in opioid signalling, and may be only involved in early withdrawal, other changes such as increased oxidative stress, neuronal apotosis, receptor down regulation and dissregulation of glutamate signalling probably underline long term alterations that lead to depression and risk of relaps even years after quitting opioids.
Interestingly, there air drugs that can increase CAMP levels, they are called phosphodeesterase inhibitors, a good example being ibudilast, widly used as an asmer medication in Japan, and being studied as an affective treatment for methamphetamine addiction, by reducing cravings, withdrawal induced depressive states, and supressing microglyol activation. Therefore, it has potent neuroprotective affects, along with a powerfull anti imflamitory affect, in all tissues, particularly in neurons. Contrary to the idea that increase CAMP production results in opioid withdrawal, cotreatment of animals and humans with ibudilast and morphine has shown to significantly delay opioid tolerance. However, this in my opinion, doesn't contradict the above hypothesis, but rather strengthens it by highlighting the role of other mechanisms of opioit tolerance, given the anti imflamitory, neuroprotective and anti apoptotic affects of phosphodeesterase inhibitors, whos affects are mediated by preventing the break down of camp and related neucleotide phosphates.
Hope this helps

 

[chugs]

Interesting questions, I will try to answer based on my own knowledge I gathered from reading along time ago.
first of all, opioid receptors, particularly the mu subtype are g protein coupled receptors, and many of their downstream affects, that is the affect inside the neuron, relies, on second messengers a key one being cyclic adenosine monophosphate or CAMP.
A well known affect of mu opioid receptors is to inhibit the enzyme adenilate cyclase, rapidly reducing intracellular CAMP levels. This is known to mediat many of the affects of opioid drugs like morphine. Some neurotransmitters like epinephrine and nor epinephrine, bind to receptors which function to increase CAMP levels, therefore sensitivity to these neurotransmitters is diminished in neurons targeted with strong mu opioid agonists.
However, during withdrawal, an exess of CAMP is produced due to overactivation of adenilate cyclase, resulting in supper sensitivity to adrenalin and hyperexitable neurons. Also, it must be noted that CAMP, is only one molecule involved in opioid signalling, and may be only involved in early withdrawal, other changes such as increased oxidative stress, neuronal apotosis, receptor down regulation and dissregulation of glutamate signalling probably underline long term alterations that lead to depression and risk of relaps even years after quitting opioids.
Interestingly, there air drugs that can increase CAMP levels, they are called phosphodeesterase inhibitors, a good example being ibudilast, widly used as an asmer medication in Japan, and being studied as an affective treatment for methamphetamine addiction, by reducing cravings, withdrawal induced depressive states, and supressing microglyol activation. Therefore, it has potent neuroprotective affects, along with a powerfull anti imflamitory affect, in all tissues, particularly in neurons. Contrary to the idea that increase CAMP production results in opioid withdrawal, cotreatment of animals and humans with ibudilast and morphine has shown to significantly delay opioid tolerance. However, this in my opinion, doesn't contradict the above hypothesis, but rather strengthens it by highlighting the role of other mechanisms of opioit tolerance, given the anti imflamitory, neuroprotective and anti apoptotic affects of phosphodeesterase inhibitors, whos affects are mediated by preventing the break down of camp and related neucleotide phosphates.
Hope this helps

Hi Neuroprotection,

A very apt name. To be frank I've moved on since making this post and I can see that from the primary cause of Opiate withdrawals is the activation of TL4 by M3G a metabolite of heroin. So technically they have nothing to do with the absences of opiates and they don't have anything to do with addiction.

If you could take an opiate that didn't activate TL4 or you suppressed TL4 then you could effectively avoid what its incorrectly called withdrawals.

I still don't understand why people aren't screaming this from their roofs.


- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783351/ is the article that has a part of this research. Really though you need to read all of Watkins and Hamiltons research on this that they've done over the past 7 years.