Request for Inosine startup effects experiences

[Violeta]

The other input pathway to adensoine is from AMP (via the 5-nucleotidase enzyme), which is something we haven't explored, maybe a project for tomorrow. @Violeta noted earlier that Caffeine inhbits Phosphodiesterase

Polygala tenuifolia is an adenosine monophosphate phosphodiesterase inhibitor, too.

Here's an article about it. It's a pdf, I couldn't copy the title.

https://www.jstage.jst.go.jp/article/cpb1958/30/6/30_6_2020/_pdf

 

[Violeta]

A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome
This study looked at 3 metabolic phenotypes in 83 people with ME/CFS (MEall, ME1, ME2, ME3) and 35 healthy controls (HC). The study mentions adenosine being increased in pwME. When I pulled the sublemental data for the study, I found this showing an almost 5 fold increase in adenosine pwME.

Where is all the adenosine coming from?

Found one thing that raises adenosine, ethanol.

Since adenosine levels are increased in response to acute ethanol exposure, adenosine-regulated inhibition of glutamate release partially accounts for the intoxicating effects of ethanol.

"As a neuromodulator, one of the main functions of adenosine is to inhibit glutamate release via presynaptic A1 receptors in the nucleus accumbens (NAc)."



Studies have also shown that adenosine is released [3] from cortical slices and inhibits acetylcholine (ACh) release from cholinergic terminals evoked by axonal stimulation via activation of theophylline-sensitive receptors.

And then:
Adenosine agonists acting upon A2A receptors instead counteract the effect of dopamine acting upon D2R. In fact, activation of A2A receptors leads to a decrease in receptor affinity for dopamine agonists, especially of the high- affinity state

I'm trying to figure out if it has anything to do with orthostatic hypotension.

 

[Violeta]

magnesium is the cofactor for adenosine kinase,

I have been trying for years to figure out why an extremely low carb diet would bring on herpesvirus1 and/or shingles attack. This happened to me several times. The diet would have been extremely low in magnesium.

Thank you so much for this piece of information, @Shanti1.

 

[Violeta]

Just saw something about adenylate as a result of looking up adenosine and ammonia.

Ammonia raises AMP deaminase and adenosine deaminase,
That depletes adenylate reserves
And then there is a downgrading of conversion of to cAMP.

Is ammonia the culprit? Any thoughts or corrections?

We studied the effect of acute ammonia poisoning and CCl4-induced subacute hepatitis on activities of AMP deaminase and adenosine deaminase in rat liver. Both models of liver failure were accompanied by an increase in activities of AMP deaminase and adenosine deaminase in the cytoplasmic fraction of the liver (by 2.4–4.2 times compared to the control). A direct correlation was found between activities of AMP deaminase and adenosine deaminase. We believe that two parallel pathways of AMP degradation are activated simultaneously, which leads to rapid depletion of adenylate reserves under pathological conditions.

Adenylate cyclase (AC) is the only enzyme that generates the second messenger 3′:5′-adenosine monophosphate (cyclic AMP) out of ATP. Cyclic AMP modifies cell function in virtually all eukaryotic cells through the activation of cyclic AMP-dependent protein kinase or through cyclic AMP-gated ion channels.

 

[Violeta]

Kefir!

Kefir protects the liver against high fructose corn syrup induced phosphodiesterase hyperactivity​

https://www.degruyter.com/document/doi/10.1515/tjb-2021-0180/html?lang=en

HFCS upregulated hepatic PDEs while repressed primary insulin signaling elements at gene and protein levels. It also augmented cPLA2 and IGF-1Rα expression. Kefir suppressed the phosphodiesterases and normalized the insulin signaling, and down-regulated cPLA2 and IGF-1Rα in the liver of HFCS-fed rats.

I imagine this would be true for other situations besides high dietary fructose corn syrup.

 

[Violeta]

Oxidative stress increases PDE5 expression and activity.

So oxidative stress might be one reason why PDE5 inhibitors might be needed.

Hoping that polygala tenuifolia inhibits phosphodiesterase by increasing anti-oxidants and lowering oxidative stress.

"Polygala tenuifolia significantly increased acetylcholine and APT significantly increased acetylcholine and choline acetyltransferase levels in the hippocampus and prefrontal cortex of scopolamine-induced mice. Additionally, treatment with polygala t. significantly increased BDNF and IL-10 levels, and decreased IL-1β and acetylcholinesterase levels in the same mice. Furthermore, APT significantly increased SOD activity and GSH content, and decreased MDA levels in brain tissue. These results indicated that polygala may ameliorate learning and memory impairment by regulating cholinergic activity, promoting BDNF and inhibiting neuroinflammation and oxidative stress."

 

[Shanti1]

Polygala tenuifolia is an adenosine monophosphate phosphodiesterase inhibitor, too.

Nootropic Depot sells it as a supplement

I'm trying to figure out if it has anything to do with orthostatic hypotension.

When given by IV adenosine can lower blood pressure, but I'm not sure how much it influences blood pressure in the levels at physiological levels. We know adenosine build up in the brain causes sleepiness, but it doesn't cross the blood-brain-barrier, so if high levels of adenosine in the brain impacted BP, it would have to do it at the CNS level. Somewhere in this thread I posted a study showing elevated peripheral levels of adenosine, but I don't know if this elevation would be enough to bring on hypotension. It is a good question.

 

[Blazer95]

Inosine is a immunostimulant correct?

I would be Interested If anybody knows wether inosine stimulates il-4 and/or il-17 or supresses it.

Despite many immunomodulative substances being il-17 decreasing wich May be wanted for some its counterproductive for the Subset of ME/CFS patients with too Low il-17 secretion.
If we Take oxymatrine for example, IT often marketed as the ideal th1 stimulant (wich is correct according to my information) while leaving out of context it can massivly inhibit th17 and th2 aswell.

Interestingly enough though <3 years of illness the th17 secretion seems to be elevated and in 3+ years of illness its becoming decreased, wich indicates an exhaustion instead of a simple deficiency. So while being careful with intensive th17 Stimulation (wich May worsen Symptoms of th17 exhaustion) we should consider avoiding further th17 supression as th17 deficiency is linked to chronic reoccuring infections such as Candida albicans.

Cheerio

 

[cfs since 1998]

I got bad joint pain on inosine for a few months. I even developed a bruise on my back and a visually bulging disc after hitting a pothole while driving when I was taking it. Took almost a year after stopping it before my joints went back to normal.