2626 replies to this topic

[cylon]

I'm tempted to start another thread since this one doesn't seem to be getting any more attention but...

 

Does anyone know how to delay the onset of physical fatigue after about 8 hours of dosing with CILTEP? It's possible its something else in my regimen but there are 3 things I usually experience when dosing with my custom CILTEP stack (following the directions at the beginning of this thread)

1-slight to moderate increase in focus and productivity. I realize this is somewhat subjective, and some might attribute this to placebo. I can only relay what I experience. I'm also not 100% sure this ins't just the effect of the Forskolin by itself, or if there is an actual synergy happening between the ingredients, but I remain guardedly optimistic about using this semi regularly.

2-noticeable drop in physical energy after approximately 8 hours. Concentration is fine. Just feel very fatigued after having plenty of energy all day

3-Sudden drowsiness after approx 12hours.

The latter I don't have a problem with as it just means I'm in bed an hour earlier...and up and hour earlier than normal. But the physical fatigue I feel at the end of the day is a nuisance. Any suggestions?

 

[gizmobrain]

No need for a new thread, as this issue has been discussed.

Here's one from the old days

Just finished reading this entire thread. Was a cause for the tiredness some people experienced ever identified?

http://www.ncbi.nlm.nih.gov/pubmed/2420646']
A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor. A study with forskolin and its analogs.

Abstract

Forskolin, an activator of adenylate cyclase, and its analogs were studied on the nicotinic acetylcholine receptor-ion channel complex (AChR) of rat and frog skeletal muscles. At nanomolar concentrations, forskolin caused desensitization of the AChR located at the junctional region of innervated and the extrajunctional region of chronically denervated rat soleus muscles. The desensitization of the AChR occurred without alteration of the conducting state (channel lifetime, conductance or bursting) as shown by single channel currents. Accordingly, forskolin decreased the peak amplitude of the repetitive evoked endplate currents in frog sartorius muscles. These findings taken together with the good correlation found between the effects of forskolin and its analogs on the desensitization of the nicotinic AChR and their ability to activate adenylate cyclase suggested a possible involvement of phosphorylation of AChR via cyclic AMP on the desensitization process.
PMID: 2420646

→ source (external link)

Essentially: desensitized nAChR's.

A couple days break with a dose of Galantamine seems to be enough to undo the desensitization (SmartPowders Galantamine works great for this, and is much cheaper than most sources). Also, keeping your dosage of Forskolin low (~5mg) can nearly prevent it from happening, while maintaining most of the positive effects and eliminating most of the negatives.

Today was my first day with the 98% Forskolin extract. Feels much cleaner and had no effect on my digestive tract what so ever. I think we have a winner!

Also, I find that n-acetyl tyrosine and making sure my b-vitamins and applicable minerals levels remain steady is pretty important for maintaining energy levels.

Edited by zrbarnes, 10 March 2015 - 03:09 AM.

[cylon]

Thanks. May I ask where did you get your Forskolin and how did you determine exactly 5mg? Will try adding a small amount of LTyrosine (<100mg?) and possibly supplementing with more ACAR in the afternoon to see if it helps with delaying energy fatigue.

[Metagene]

Not a CILTEP believer, just following up zrbarnes.

Forskolin alters acetylcholine receptor gating by a mechanism independent of adenylate cyclase activation.

The diterpene forskolin activates adenylate cyclase in a receptor-independent fashion and is commonly used to obtain a rapid elevation of intracellular cAMP levels. Application of 10-20 microM forskolin to Xenopus oocytes that express Torpedo nicotinic acetylcholine (ACh) receptors leads to an acceleration in the decay of ACh-elicited currents, which could be taken as evidence for modulation of ACh receptor gating by cAMP-dependent protein kinase. However, the effect is not mimicked by phosphodiesterase inhibitors or intracellular injection of a cAMP analog. In addition, 1,9-dideoxyforskolin, which is unable to activate adenylate cyclase, has a similar effect. Finally, the action of forskolin is rapidly reversible, with full onset and recovery occurring within the exchange time of the recording chamber. These results suggest that forskolin is a potent local anesthetic and that this property of this widely used compound must be taken into account when using it to study ion channel modulation.

http://www.ncbi.nlm....pubmed/2459589/

Edited by Metagene, 10 March 2015 - 03:08 PM.

[Metagene]

Modulation of acetylcholine receptor desensitization by forskolin is independent of cAMP.


Biochemical and electrophysiological studies suggest that adenosine 3',5'-monophosphate (cAMP)-dependent phosphorylation of the nicotinic acetylcholine receptor channel is functionally significant because it modifies the receptor's rate of desensitization to acetylcholine. In studies that support this conclusion researchers have used forskolin to stimulate cAMP-dependent phosphorylation in intact muscle. It is now shown that although forskolin facilitated desensitization in voltage-clamped rat muscle, this effect was not correlated with the abilities of forskolin and forskolin analogs to activate adenylate cyclase or phosphorylate the receptor. Furthermore, elevation of intracellular cAMP or addition of the catalytic subunit of A-kinase failed to alter desensitization. Therefore, in intact skeletal muscle, cAMP-dependent phosphorylation does not modulate desensitization.

http://www.ncbi.nlm....2420646/related

[cylon]

FWIW, need to confirm with repetition, but so far it seems like extra ALCAR after lunch is helping me avoid the physical fatigue towards end of day (roughly 8 hours after 7:30am CILTEP dosage) Anyone else experience this? Before Abelard included ALCAR in CILTEP wasn't he dosing with it in afternoon?

 

'For mitigating forskolin's effects on Acetylcholinesterase:

800mg ALCAR (Generally 200mg of ALCAR for every 1mg of forskolin)'

[cylon]

I did however wake the following morning with a slight headache, so somethings still need tweaking in my custom stack. What needs to be tweaked, added, removed in the following? Or I was wondering if my morning headache could be related to concurrent Piracetam use and choline depletion. Dosed 800mg Piracetam the day before.

 

MORNING

10mg forskolin

400mg Artichoke extract

500mg ALCAR

500mg lPhenylanine

100mg lTyrosine

100mg B6

 

AFTERNOON

500mg ALCAR

 

EVENING(sleep stack)

500mg Magnesium combo(taurate, malate,citrate)

LTheanine 100mg

5HTP 15mg

Melatonin 1.5mg

Edited by cylon, 11 March 2015 - 10:39 AM.

[abelard lindsay]

I did however wake the following morning with a slight headache, so somethings still need tweaking in my custom stack. What needs to be tweaked, added, removed in the following? Or I was wondering if my morning headache could be related to concurrent Piracetam use and choline depletion. Dosed 800mg Piracetam the day before.

 

MORNING

10mg forskolin

 

 

More than 5mg of forskolin is not advised.  Less is more.  FYI, all this is on the first page of the thread or over on my ciltep page at abelardresearch.com.

[cylon]

Thanks Justin

[cylon]

With the Natural Stacks is there any noticeable effect using a single pill? Or do you need to dose with 3 pills to get any benefit? The actual amounts per pill seem quite low.

[yborcity]

Anyone buys his BetterSports C-Bolic forskolin  via bodybuilding.com in EEC? it seems that this online merchant discontinued this brand lately and i do not know any other online merchants that delivers to europe, any insights? 

[cylon]

re 

http://www.longecity...-33#entry544100

 

 

Can anyone make sense of this pubmed study?

http://www.ncbi.nlm....pubmed/23127850

 

Any cause for concern?

 

 

[thereisway]

With the Natural Stacks is there any noticeable effect using a single pill? Or do you need to dose with 3 pills to get any benefit? The actual amounts per pill seem quite low.

I think I notice a cognitive boost but not enough to aid my studies. Maybe just enough to keep me in an improved mood.

[nicklesprout]

i was interested in CILTEP for Benzo Withdrawal, but then i read this article on Withdrawal and LTP:

 

http://www.benzobudd...p?topic=85498.0

 

makes it sound like LTP is something to be avoided for us benzo PAWSers. thoughts?

[chung_pao]

Abelard,

Made a discovery while resuming the use of Artichoke, for other than nootropic purposes (PXR activation and detoxification. Exploring other mechanisms.).
Thought you'd be interested.

*The brand that provides the greatest improvement in mental performance is - and this is by far: NOW Foods (used at the original 450-900 mg).

Jarrow foods comes at a second place. I had originally used Jarrow, but had run out, and NOW Foods' product was most convenient to order.
But their comparison is ridiculous (like 100% vs. 65%).
And Planetary Herbals (brand name) is even less effective for mental performance (like 100% vs 65% vs 40%).

NOW Foods Artichoke doesn't produce the same inhibition of working memory and impairment of verbal fluency I'd complained about earlier, and that I've seen other people experience. Also the whole "debunking CILTEP" deal could be because people use other brands with differing pharmacological compositions.

Thoughts?

[thereisway]

Been taking Ciltep off and on for abt 3 months and I just ordered 2 more bottles 1 month ago but it looks like I have no use for ciltep no more.

 

While on Ciltep my handwriting improved tremendously to the extent that my fellow students kept awwing at how well and neatly I was writing.

It feels like a Right Brain stack and less left brain.

In terms of Academic performance its like it made me a bit dumper. As usual I would easily understand topics and procedural memory was quite ok but I kept forgeting simple things and reproducing learned material in the exam room felt a bit slowed and foggy. Basically the cramming memory was fucked up by this stack. This is the reason I dropped it.

Fortunately, I keep my good handwriting

 

 

[whiteredflower]

to get good effects, you need to decrease noraderline

Quercetin can do this.

[ricko321]

Im not sure but i think porn has to with dopamine receptors,becouse just from couple days of not watching i could feel the effects of artichoke plus turmeric i feel a very huge dopamine rush which i was tryng to get with porn

[Lancelott]

This thread has been abandoned for a while, but i am doing some research about CILTEP, and i'm really interested on the subject

Thinking on how LTP depends on NMDA receptors, and it takes a while for it to open, i was just wondering if an ampakine would help in this stack's synergy

I was thinking about noopept, since it has good affinity to the NDMA receptors as well.. I mean, that's the focus isn't it? more (Ca++) + more cAMP (=more CREBS), more LTP right? I mean, thats the late phase of LTP..

Does anybody agree/disagree? any thoughts?

 

I am about to buy forskolin and artichoke, and add this to my usual stack [caffeine 100mg; l-theanine 200mg; l-tyrosine 100mg; ALCAR 500mg; noopept 10mg].. I would take the theanine off because of the anxiolytic effects from reports, but it's already capsuled, so whatever.. the only thing is capsuled separately is the ALCAR, but i read something about it helping to avoid the fatigue.. And it also contributes to acetilCoA formation, so, as noopept is also an AChR modulator, i should give it a try..

 

I'll relate it once i get it.. but i would really like opinions!

Thanks!

[surpriza]

hello guys,

 

i`ve read all about ciltep and i`m confused... after a month i dont feel any effect and i need some opinions, maybe it`s to mucht on my daily stack:

 

morning:

3 pills ciltep

300mg - alpha gpc

1200mg - piracetam

2g - glutamine

120mg gingko biloba

coconut oil + 500mg dha/250 epa

 

 

evening

3 pills magtech 

2 pills baccopa monieri

2 pills panax ginseng

1g lions mane

 

 

i also take multivitamin and mineral, whey protein , casein protein, lysina, creatina with beta-alanina,and some mix of biogreens.

 

thanks of any advice!

[Mian Ali Ismail]

http://www.prnewswir...-300280725.html

 

Possible treatment for Alzhimers.

 

CAN ANYYONE HERE TELL ME ABOUT ITS MECHANISM OF ACTION ?

 

The results, published in the Journal of Medical Case Reports, details the promising results that the research duo of Victor and George Tetz had in treating a 77-year-old Alzheimer's patient with the repurposed medication deoxyribonuclease I, an enzyme approved by the U.S. Food and Drug Administration for the treatment of mucus buildup in cystic fibrosis patients.

"Our results show potential for reversing the effects of a disease that dramatically impacts not only millions of patients around the world, but also their families," said George Tetz, scientific officer, at HMI.  "Our experimental drug has given one patient a new lease on life, and now we are continuing with our tests with the hopes of reversing the devastating effects of Alzheimer's disease and other incurable diseases like dementia and Parkinson's."

According to the published case study, the male patient had been diagnosed with dementia and behavioral disturbance secondary to late-onset Alzheimer's disease 30 months before the researchers first saw him. He had been undergoing routine treatment, but his cognitive condition continued to deteriorate and he had rapidly progressing amnesia and behavioral changes.

The patient was unable to remember his name or family members, among other things, and had been diagnosed as terminal when his family agreed to try DNase I. Just two days after treatment began, improvements were seen. And he was soon able to recognize family members, dress himself, tie his shoelaces, feed himself and walk and ride an exercise bike.

"Treatment with DNase I allowed the patient to withdraw from a terminal state and resulted in significant improvements in cognitive and behavioral function, including the ability to walk and perform everyday tasks with near independence," said Victor Tetz, scientific advisor at HMI.

HMI, a non-profit research organization, is working to convert its work into a drug to help treat dementia, Alzheimer's and Parkinson's diseases.

Alzheimer's disease is the most common cause of dementia and is characterized by a progressive loss of brain tissue leading to amyloid-b accumulation and severe decline in cognitive function. 

More than 5 million Americans are living with Alzheimer's disease. The cause of Alzheimer's disease is poorly understood, and available treatments are limited in their efficacy, particularly for patients with more severe symptoms.

 

Edited by Mian Ali Ismail, 09 June 2016 - 02:26 PM.

[christianme]

Hey,

 

Is anyone here experimenting on how to combine this stack with the Uridine stack, or are you guys content with the CILTEP stack alone?  

[lostfalco]

Hey,

 

Is anyone here experimenting on how to combine this stack with the Uridine stack, or are you guys content with the CILTEP stack alone?  

Yeah, I've been doing this for the past few months or so with extremely good results. 

 

I've basically created my own ultra-effective version of CILTEP. 

 

I use low level laser therapy (LLLT) to increase cAMP.

 

I use ibudilast (a PDE4 inhibitor) to inhibit the breakdown of cAMP (luteolin has low absorption and is quickly metabolized, although a liposomal or intranasal version might work well).

 

I've patterned my uridine stack after Souvenaid (I buy my own ingredients). Here are all the ingredients and dosages. https://www.souvenai...ormation-Sheet/

 

 

http://www.ncbi.nlm....pubmed/21184127

 

Lasers Med Sci. 2011 May;26(3):389-400. doi: 10.1007/s10103-010-0874-x. Epub 2010 Dec 24.

Low-level laser therapy (LLLT) acts as cAMP-elevating agent in acute respiratory distress syndrome.

de Lima FM1, Moreira LM, Villaverde AB, Albertini R, Castro-Faria-Neto HC, Aimbire F.

Author information

 

Abstract

The aim of this work was to investigate if the low-level laser therapy (LLLT) on acute lung inflammation (ALI) induced by lipopolysaccharide (LPS) is linked to tumor necrosis factor (TNF) in alveolar macrophages (AM) from bronchoalveolar lavage fluid (BALF) of mice. LLLT has been reported to actuate positively for relieving the late and early symptoms of airway and lung inflammation. It is not known if the increased TNF mRNA expression and dysfunction of cAMP generation observed in ALI can be influenced by LLLT. For in vivo studies, Balb/c mice (n = 5 for group) received LPS inhalation or TNF intra nasal instillation and 3 h after LPS or TNF-α, leukocytes in BALF were analyzed. LLLT administered perpendicularly to a point in the middle of the dissected bronchi with a wavelength of 660 nm and a dose of 4.5 J/cm(2). The mice were irradiated 15 min after ALI induction. In vitro AM from mice were cultured for analyses of TNF mRNA expression and protein and adenosine3':5'-cyclic monophosphate (cAMP) levels. One hour after LPS, the TNF and cAMP levels in AM were measured by ELISA. RT-PCR was used to measure TNF mRNA in AM. The LLLTwas inefficient in potentiating the rolipram effect in presence of a TNF synthesis inhibitor. LLLT attenuated the neutrophil influx and TNF in BALF. In AM, the laser increased the cAMP and reduced the TNF-α mRNA. LLLT increases indirectly the cAMP in AM by a TNF-dependent mechanism.

 

http://www.ncbi.nlm....pubmed/16313925

 

Life Sci. 2006 May 1;78(23):2663-8. Epub 2005 Nov 28.

Preferential inhibition of human phosphodiesterase 4 by ibudilast.

Huang Z1, Liu S, Zhang L, Salem M, Greig GM, Chan CC, Natsumeda Y, Noguchi K.

Author information

Abstract

Ibudilast ophthalmic solution exhibited an improved clinical efficacy over cromoglycate in the treatment of allergic conjunctivitis. To further characterize its principal mode of action, the phosphodiesterase (PDE) inhibitory profile of ibudilast has been examined using human recombinant enzymes. Ibudilast, but not the other commonly used anti-allergic ophthalmic solutions including cromoglycate, ketotifen, tranilast and levocabastine, potently inhibits purified human PDE4A, 4B, 4C and 4D with IC50 values at 54, 65, 239 and 166 nM, respectively. Ibudilasteffectively blocks lipopolysaccharide (LPS)-induced tumor necrosis factor (TNFalpha, IC50 = 6.2 microM) and N-formyl-Met-Leu-Phe (fMLP)-induced leukotriene (LT) B4 biosynthesis (IC50 = 2.5 microM) in human whole blood, which are 3 and 6-fold more potent than cilomilast, respectively. The attenuated inflammatory and allergic responses from the potent and preferential PDE4 inhibition of ibudilast may have contributed significantly to its beneficial pharmacological responses and distinguishes ibudilast from the other ophthalmic solutions in the treatment of ocular allergy.

 

 

http://www.ncbi.nlm....pubmed/27250850

 

Neuromolecular Med. 2016 Jun 1. [Epub ahead of print]

Synaptogenesis: Modulation by Availability of Membrane Phospholipid Precursors.

Cansev M1.

Author information

Abstract

Phospholipids are the main constituents of brain membranes. Formation of new membranes requires that uridine, the omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA), and choline, the three circulating precursors of major phospholipids, interact via the Kennedy pathway. Supplementation of laboratory rodents with uridine, DHA and choline enhances the amount of brain membranes as well as synaptic proteins and increases the number of dendritic spines, the essential cytological precursor of new synapses. Hence, the newly formed membranes are utilized for synaptogenesis which underlies increased synaptic functioning evidenced by enhanced neurotransmission and cognition. In addition, this supplementation ameliorates the degeneration in a rat model of Parkinson's disease and mouse models of Alzheimer's disease (AD) when used in combination with several vitamins and cofactors. Hence, accumulating evidence shows that increasing the availability of phospholipid precursors, vitamins and cofactors to the brain through dietary supplementation enhances the formation of new synapses and provides protection under neurodegenerative conditions. The combination has been tested in clinical trials and a medication has been marketed for early-stage AD patients.

 

http://www.ncbi.nlm....les/PMC4490655/

 

"Moreover, less than 10% of orally ingested flavonoids are absorbed (Passamonti et al., 2009; Thilakarathna and Rupasinghe, 2013) and are extensively metabolized to inactive ingredients in the liver (Chen et al., 2014)."

 

Front Neurosci. 2015 Jul 3;9:225. doi: 10.3389/fnins.2015.00225. eCollection 2015.

Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin.

Theoharides TC1, Stewart JM2, Hatziagelaki E3, Kolaitis G4.

Author information

Abstract

Brain "fog" is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain "fog" characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as "minimal cognitive impairment," an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain "fog" may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain "fog" in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain "fog."

 

Edited by lostfalco, 24 June 2016 - 03:43 PM.

[abelard lindsay]

 

Hey,

 

Is anyone here experimenting on how to combine this stack with the Uridine stack, or are you guys content with the CILTEP stack alone?  

Yeah, I've been doing this for the past few months or so with extremely good results. 

 

I've basically created my own ultra-effective version of CILTEP. 

 

I use low level laser therapy (LLLT) to increase cAMP.

 

I use ibudilast (a PDE4 inhibitor) to inhibit the breakdown of cAMP (luteolin has low absorption and is quickly metabolized, although a liposomal or intranasal version might work well).

 

I've patterned my uridine stack after Souvenaid (I buy my own ingredients). Here are all the ingredients and dosages. https://www.souvenai...ormation-Sheet/

 

 

LostFalco:  How does ibudilast compare to Zembrin?  The Zembrin CILTEP stack works great for studying, but I don't take it regularly since it makes me dislike talking to people.  

 

I have combined the happy stack with CILTEP and gotten good results.  The only caveat is that I have to take it with a gram or so of tryptophan or I feel unusually depressed the next day.

 

Cheers,

 

Abelard.

[lostfalco]

 

LostFalco:  How does ibudilast compare to Zembrin?  The Zembrin CILTEP stack works great for studying, but I don't take it regularly since it makes me dislike talking to people.  

 

I have combined the happy stack with CILTEP and gotten good results.  The only caveat is that I have to take it with a gram or so of tryptophan or I feel unusually depressed the next day.

 

Cheers,

 

Abelard.

 

Hey, what's up Abelard? Glad to see you're still around!

 

Thanks again for bringing this nootropic mechanism of action to the community. 

 

I've had much better results with ibudilast than zembrin for PDE4i. Ibudilast makes me extremely focused but also puts me in a good mood so I don't tend to avoid people. I could see how it might cause people avoidance for some though. I tend to notice that I find math, physics, engineering, etc. even more fascinating than I normally do when I'm taking it. Worth a one time experiment for most people imo just to see how it affects them. 

[gizmobrain]

 

LostFalco:  How does ibudilast compare to Zembrin?  The Zembrin CILTEP stack works great for studying, but I don't take it regularly since it makes me dislike talking to people.  

 

 

 

I have combined the happy stack with CILTEP and gotten good results.  The only caveat is that I have to take it with a gram or so of tryptophan or I feel unusually depressed the next day.

 

Cheers,

 

Abelard.

 

 

It's like a CILTEP pioneer reunion... ( I believe we are the 2 longest CILTEP guinea pigs, no?) Congrats on the patent! I got a little ticked off that some jerk lawyer was patenting something I feel emotionally involved with, until I realized he was your lawyer, then I was okay with it . Hopefully it brings you guys some opportunities for clinical studies. I'd love to know exactly how it works, beyond the theorizing.

[abelard lindsay]

 

 

LostFalco:  How does ibudilast compare to Zembrin?  The Zembrin CILTEP stack works great for studying, but I don't take it regularly since it makes me dislike talking to people.  

 

 

 

I have combined the happy stack with CILTEP and gotten good results.  The only caveat is that I have to take it with a gram or so of tryptophan or I feel unusually depressed the next day.

 

Cheers,

 

Abelard.

 

 

It's like a CILTEP pioneer reunion... ( I believe we are the 2 longest CILTEP guinea pigs, no?) Congrats on the patent! I got a little ticked off that some jerk lawyer was patenting something I feel emotionally involved with, until I realized he was your lawyer, then I was okay with it . Hopefully it brings you guys some opportunities for clinical studies. I'd love to know exactly how it works, beyond the theorizing.

 

 

Nice to see you all around.    Exciting stuff is in the works with regards to further developing the science of CILTEP.  We should have some announcement about that later this year.  

 

Meanwhile, at the summit of Mt. Everest (not photoshopped!):

 

 mteverest.jpg   88.65KB   20 downloads

Edited by abelard lindsay, 24 June 2016 - 08:12 PM.

[gizmobrain]

Awesome. 

 

Just to contribute to some science-y stuff for the thread, forskolin has some pretty interesting effects on the vitamin D pathway.

 

http://www.ncbi.nlm..../pubmed/6317364

 

 

 

Forskolin increases 1,25-dihydroxyvitamin D3 production by rat renal slices in vitro.

Abstract

Renal production of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] from 25-hydroxyvitamin D3 (25OHD3) is increased by PTH. The complete mechanism by which PTH modulates renal 25OHD3 metabolism is not known, but there is some evidence that the stimulation of renal cAMP production by PTH may be important. Therefore, we have used forskolin, a direct activator of adenylate cyclase in the intact tissue, to further investigate the role of cAMP in regulating renal 25OHD3 metabolism. The effect of forskolin on renal 25OHD3 metabolism and renal adenylate cyclase activity was measured using isolated renal slices from thyroparathyroidectomized rats previously fed a vitamin D-deficient, low calcium diet. Forskolin added to renal slices in vitro for 4 h increased renal 1,25-(OH)2-D3 production in a concentration-dependent manner. In separate experiments, forskolin was found to increase tissue cAMP in a concentration-dependent manner when added for 5 min. The concentration of forskolin necessary for half-maximal stimulation of adenylate cyclase was 10 microM, and that needed for half-maximal stimulation of 1,25-(OH)2-D3 production was 1 microM. PTH added to renal slices also increased renal 1,25-(OH)2-D3 production, but the effects of PTH and forskolin were not additive. Inclusion of 1,25-(OH)2-D3 in the incubation medium blocked the effect of forskolin on 1,25-(OH)2-D3 production, but it did not block the effect of forskolin on tissue cAMP content. These studies support the concept that forskolin and PTH modulate renal 25OHD3 metabolism though a cAMP-dependent pathway. However, this pathway may be further regulated at sites distal to cAMP production by compounds such as 1,25-(OH)2-D3.

 

http://www.ncbi.nlm..../pubmed/1314957

 

 

 

Cyclic adenosine 3',5'-monophosphate up-regulates 1,25-dihydroxyvitamin D3 receptor gene expression and enhances hormone action.

Abstract

We have previously shown that the abundance of vitamin D receptors (VDR) in cultured cells is increased by mitogens such as serum and growth factors, whereas activation of protein kinase-C (PK-C) causes inhibition of VDR gene expression. This study examines the effect of the cAMP-activated protein kinase-A (PK-A) second messenger system on VDR abundance and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] action. Elevation of intracellular cAMP levels in NIH-3T3 mouse fibroblasts by forskolin or (Bu)2cAMP caused a substantial (8- to 12-fold) increase in VDR abundance, as measured by ligand binding and Western blot analysis. The time course of the forskolin effect on VDR expression was complex. An early rise in VDR abundance occurred at 4 h, followed by a decrease and then a broad secondary rise at 18 h. At the mRNA level, forskolin caused a rapid rise in VDR transcripts after 1 h of exposure, a peak at 2 h, followed by a decline and a subsequent increase at 15 h. Activation of PK-C with the phorbol ester phorbol myristate acetate abolished the forskolin-induced increase in VDR protein and mRNA abundance. NIH-3T3 cells were stably transfected with phOC-CAT, a plasmid carrying a human osteocalcin promoter fragment containing the vitamin D response element fused to the reporter gene chloramphenicol acetyl transferase (CAT). 1,25-(OH)2D3 treatment of transfected cells induced a dose-dependent increase in CAT activity. Up- or down-regulation of VDR in these transfected cells by forskolin or phorbol myristate acetate pretreatment, respectively, resulted in corresponding enhancement or attenuation of 1,25-(OH)2D3-inducible CAT activity.

 

 

[bzyb]

 

Nice to see you all around.    Exciting stuff is in the works with regards to further developing the science of CILTEP.  We should have some announcement about that later this year.  

 

Meanwhile, at the summit of Mt. Everest (not photoshopped!):

 

mteverest.jpg

 

Wow nice new developments.  Happy stack and ibudilast can help with the anti-social aspects of CILTEP and hopefully lower slight agitation?  Where to buy ibudilast, (not on amazon) seems like an all-round healthy supplement?

Nice picture, is it you or a friend (I can see have long hair)? Everest seems too tough to do, maybe better to just fly to the top.

Edited by bzyb, 27 June 2016 - 02:53 AM.

[abelard lindsay]

 

 

Nice to see you all around.    Exciting stuff is in the works with regards to further developing the science of CILTEP.  We should have some announcement about that later this year.  

 

Meanwhile, at the summit of Mt. Everest (not photoshopped!):

 

mteverest.jpg

 

Wow nice new developments.  Happy stack and ibudilast can help with the anti-social aspects of CILTEP and hopefully lower slight agitation?  Where to buy ibudilast, (not on amazon) seems like an all-round healthy supplement?

Nice picture, is it you or a friend (I can see have long hair)? Everest seems too tough to do, maybe better to just fly to the top.

 

 

A very adventurous and fit Natural Stacks customer sent that photo in.  I went for a 4 mile run yesterday if that counts for anything.