I have asked this question several times over the years but have never gotten an answer. It is not a hard question and should be easily answered, but for some reason it is not. Since there are some new minds here now, I will ask it again.

We are told that adrenaline is made from noradrenaline which, in turn, is made from dopamine. Enzymes and co-factors are required to enable the reactions.

My question is - If one has a borderline deficit in the supply of any of these chemicals and one encounters a situation that requires the production of adrenaline beyond the normal reserve, what happens? Do we deplete dopamine to create the more essential adrenaline? And what if this is a chronic problem?

Most importantly, why is it so difficult to find the answer to such a basic question?

I know only one thing...when I get in a stress situation, dopamine seems to hit bottom and I can get symptoms (hand tremor or sometimes just hand restlessness or leg restlessness , or my singing voice is gone ) when a couple minutes before I was perfectly ok. I think Rhodiola is helping this though. I was in a stressful situation today and faced it with relative calmness and without symptoms..still haven't taken fava tincture today. COOL (very cool with the temps below freezing all day and having to go out)

what if the alchemy is highly individualized ? I too am wondering about this and it may not be simply a deficit of supply rather a sort of grooved response pattern governed by memory?

I like the fava pod juice because I suspect it contains enzymes that assist levadopa uptake - purely speculation on my part

it is good to become aware of when one releases cortisol and when one releases endorphins - its hard to discern some ttimes for example exercise if approached with competitive motives produces cortisol even though it feels good?

I am sure you have heard of an Adrelaline High. A person perceives danger, Adreline is released allowing your heart to beat faster, and focus is suddenly stronger to handle the danger. Have you heard of a dopamine high? You have a dopaminen high when you fall in love, or have eaten your favorite comfort food. You feel contented, you are totally relaxed. Unfortunately it also makes you feel rewarded, Dopamine is a neuron that helps us learn. It rewards us if we have completed a paper on schedule. It rewards us when we help others. We encourage over eating of bad food because we are seeking that relaxed feeling. We develope addictions to gambling, shopping, etc. because we are seeking a dopamine high. We are incapable of getting it, but it doesn't stop us from trying.

Dianna

Just kidding, but I do type older than I really am.

Let me explain a little more. Our bodies gather up certain raw materials and use them to make dopamine, which is then stored in tiny containers called vesicles until needed. The amount that can be made and how fast is limited by the supply of the various raw materials available. These can be things like enzymes and cofactors and mitochondrial output of the energy needed, just for an example. When your body begins to make these substances it begins to use up the materials at individual speeds. Eventually one of those materials will run out and things will grind to a halt. The substance that runs out first and triggers the shutdown is called "the rate limiting factor."

Now, consider the neurotransmitter "norepinephrine" for a moment. Norepinephrine is made much the same way as dopamine. Raw materials are gathered and norepinephrine is made. But the funny thing abut this one is that one of the things that norepinephrine is made from is dopamine!

And look at epinephrine (aka adrenaline). In a similar fashion, one of the things that epinephrine/adrenaline is made from is norepinephrine!

Now imagine this for a minute. You have just been informed by your sensory system that that guy on the bicycle is NOT going to stop. Other parts of your mind use that info and send word that you need some serious adrenaline and you need it now.

So you send the order to the adrenals and they start making adrenaline, a special hormone that is not stored but which is made fresh as needed. The raw material for that creation of adrenaline from starts pouring in to the adrenals and you note that it is mostly another hormone called "noradrenaline".

So you are mixing adrenaline as fast as you can but, then, the noradrenaline starts running low. Since you need more of that, a message goes out, "Cap'n, I don't think those entgines can handle Warp 7!" Just checking to see if everyone is still awake.

But seriously, my point is that if we have a shortage of anything then we have to prioritize and determine who gets what. And your stash of dopamine sits at the end of a chain with adrenaline at the other end.

So we have to decide on how much of our dopamine can be sent down the chain? Actually, given that the bicycle is a threat to survival, it might make sense to send it all.

My head hurts.

i seem to remember adrenal gland transplants were tried in pd.
http://www.eurostemcell.org/factshee...tem-cells-help

since dopamine can't pass the BBB, it sure isn't leaking out of the brain and i kind of doubt dopamine precursors are actively transported out of the brain thru the BBB to be used by the adrenals. just my guess.

As you say, dopamine can't pass out by the BBB. So we have a closed system and have only the dopamine that we make. `The adrenals are presumably on the periphery so they must make a second supply of dopamine? Something still doesn't seem right....

Rick,

This is really interesting; it reminds me of that paralysis issue we both know all too well. I have been to a few doctors and my neuro insists it is not PD. I have learned that essentially I am experiencing panic attacks and it all embodies what you are saying.

If we were to assign a medical name to the sudden, profound loss of muscle tone to my legs I would say it is most akin to cataplexy which is where an emotional event triggers sudden paralysis (mostly a symptoms of narcolepsy). In essence, it is the third "forgotten" response by the limbic system to fear. Everyone thinks flight or fight but freezing is a survival technique just as well. Weird thing is cataplexy is essentially sleep paralysis occurring at the worst possible times. What happens in the brain? It is a complete shut down of norepinephrine in the locus coeruleus.

Dopamine plays a big role because it reinforces the negative feedback loop, so while initially the freezing was response to a a very traumatic event in my former work place, it only now requires a public or social setting to trigger it. It responds to propanalol and an SSRI helps prevent them, but largely I can control it with my mind.

However, regardless what my doctor says, this is very much due to our fracked up catelochamine system: norepinephrine, epinephrine and dopamine. We would not have this happening if all was copacetic. Oddly, some how my limbic system is over responsive (too much peripheral dopa or flood of norepinephrine), so I go into panic attack by just thinking of it, but then end up in a cataplexic state. I am guessing my amygdala is overly sensitive. What I don't get is why I get a flood of adrenaline to fuel the panic attack, but at same time I do not have enough to avoid the freezing. This is why the noodle legs are not immediately responsive to levodopa. Serotonin and levodopa can both produce dopamine, but norepinephrine is formed only after dopamine. I am thinking this is why it takes me 3 doses to walk again.

Makes me think that amino acid precursors are really important for some of us. I know l-tyrosine's role, but I just read that phenylalaline might be beneficial too.

Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine (The good stuff begins on page 337.)

Laura-
I seem to have largely put that dragon to rest, at least for now. Unfortunately I cannot point to one specific thing and cry "AhHa!". I will, however, list what I can think of-
1) The symptoms seemed to abate when I began two drugs - propranolol and perindopril. The latter is an ACE inhibitor. These are relatively new frontiers for PD.

This will get you started on the ACE inhibtor trail-


1. Aust N Z J Med. 2000 Feb;30(1):48-53.

The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the
clinical features of Parkinson's disease.

Reardon KA, Mendelsohn FA, Chai SY, Horne MK.

Neurosciences Department, Monash Medical Centre, Melbourne, Vic.

BACKGROUND: Animal studies have demonstrated an interaction within the striatum
between the angiotensin and dopaminergic systems. In rats, the angiotensin
converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier
and increases striatal dopamine synthesis and release. In humans, angiotensin
type 1 receptors have been found on dopaminergic neurons in the substantia nigra
and striatum. In Parkinson's disease, there is a marked reduction of these
receptors associated with the nigrostriatal dopaminergic neuron loss.
AIMS: We performed a double blind placebo controlled crossover pilot study in
seven patients to investigate the effect of the ACE inhibitor, perindopril on the
clinical features of moderately severe Parkinson's disease.
RESULTS: After a four week treatment period with perindopril, patients had a
faster onset in their motor response to L-dopa and a reduction in 'on phase' peak
dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on'
periods during their waking day in their movement diary, p=0.007. Perindopril was
well tolerated without any significant postural hypotension or renal dysfunction.
CONCLUSIONS: These results suggest that ACE inhibitors such as perindopril may
have a place in the management of motor fluctuations and dyskinesia in
Parkinson's disease and justify further study.


PMID: 10800878 [PubMed - indexed for MEDLINE]

And another


1. J Neurochem. 1999 Jul;73(1):214-9.

Effect of chronic angiotensin-converting enzyme inhibition on striatal dopamine
content in the MPTP-treated mouse.

Jenkins TA, Wong JY, Howells DW, Mendelsohn FA, Chai SY.

Howard Florey Institute of Experimental Physiology and Medicine, University of
Melbourne, Parkville, Victoria, Australia.

We have previously shown that chronic treatment with the angiotensin-converting
enzyme inhibitor perindopril increased striatal dopamine levels by 2.5-fold in
normal Sprague-Dawley rats, possibly via modulation of the striatal opioid or
tachykinin levels. In the present study, we investigated if this effect of
perindopril persists in an animal model of Parkinson's disease, the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse. C57BL/6 mice
were treated with the neurotoxin (30 mg/kg/day intraperitoneally) for 4 days and
then left for 3 weeks to allow the degeneration of striatal dopaminergic
terminals. At this time, the mice exhibited a 40% decrease in striatal dopamine
content and an accompanying 46% increase in dopamine D2 receptor levels compared
with control untreated mice. The dopamine content returned to control levels, and
the increase in dopamine D2 receptor levels was attenuated in mice treated with
perindopril (5 mg/kg/day orally for 7 days) 2 weeks after the last dose of MPTP.
When the angiotensin-converting enzyme inhibitor was administered (5 mg/kg/day
for 7 days) immediately after the cessation of the MPTP treatment, there was no
reversal of the effect of the neurotoxin in decreasing striatal dopamine content.
Our results demonstrate that perindopril is an effective agent in increasing
striatal dopamine content in an animal model of Parkinson's disease.


PMID: 10386973 [PubMed - indexed for MEDLINE]

Now, go to Wikipedia and check for ACE Inhibitors and perhaps "perindopril". That will, in turn, put you within reach of the actions of renin and aldosterone - the hormones that regulate potassium levels by sucking it up into the cell.

Speaking of the potassium shift. Remember how it usually affects young, Asian men? And do you remember that the most common trigger is a heavy carb load before sleep? Well, keep that in mind and go to Wikipedia and read "Sleep paralysis" and then "Sudden Unexpected Death Syndrome".

" Jump to: navigation, search

Sudden unexpected death syndrome, or Sudden unexpected nocturnal death syndrome (SUNDS), or Sudden Unknown Death Syndrome is sudden unexpected death of adolescents and adults, often during sleep.[1] Sudden unexplained death syndrome was first noted in 1977 among Hmong refugees in the US.[2][3] The disease was again noted in Singapore, when a retrospective survey of records showed that 230 otherwise healthy Thai men died suddenly of unexplained causes between 1982 and 1990:[4] In the Philippines, where it is referred to in the vernacular as bangungot, SUNDS affects 43 per 100,000 per year among young Filipinos. Most of the victims are young males.[5]"

"SUNDS has been cloaked in superstition. Filipinos believe ingesting high levels of carbohydrates just before sleeping causes bangungot."




It is very interesting reading. Once you get past it I'd like to know what you think.

-Rick