• Neuroscience & Pharmacology Discussion Welcome Guest
    Posting Rules Bluelight Rules
    Recent Journal Articles Chemistry Mega-Thread
    FREE Chemistry Databases! Self-Education Guide

  • N&PD Moderators: Skorpio

The P2X7 purinergic receptor

MeDieViL

MeDieViL

Bluelighter
Joined
Feb 11, 2007
Messages
3,190
Location
Belguim
The P2X7 purinergic receptor: from physiology to neurological disorders
Stephen D. Skaper 1 ,
Patrizia Debetto and
Pietro Giusti
+Author Affiliations
Department of Pharmacology and Anesthesiology, University of Padova, Padova, Italy
1 Correspondence: Department of Pharmacology and Anesthesiology, University of Padova, Largo “E. Meneghetti” 2, 35131 Padova, Italy. E-mail:[email protected]
Next Section
Abstract





Purine nucleotides are well established as extracellular signaling molecules. P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X7, have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in progressive dilation of the channel pore and the development of permeability to molecules as large as 900 Da. The P2X receptor was originally described in cells of hematopoietic origin, including macrophages, microglia, and certain lymphocytes, and mediates the influx of Ca2+ and Na+ ions, as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. The P2X7
receptor may thus represent a critical communication link between the nervous and immune systems, while providing a target for therapeutic exploitation. This review discusses the current biology and cellular signaling pathways of P2X7 receptor function, as well as insights into the role for this receptor in neurological/psychiatric diseases, outstanding questions, and the therapeutic potential of P2X7 receptor antagonism.—Skaper, S. D., Debetto, P., Giusti, P. The P2X7 purinergic receptor: from physiology to neurological disorders.
Click to expand...

http://www.fasebj.or...t/24/2/337.full

The P2X7 receptor can be targetted with the dye "brilliant blue G" wich recently has been researched for traumatic injury (
http://www.wired.com...09/07/bluerats/).

Ill post some more shit later.
 
Last edited by a moderator:
Relevance to ADD? If you can show that this is related to drug abuse/use then its cool, but right now you're just posting a random context-less abstract. This seems more like a immunology stub than anything else to me :/
 
Basically, blue FD&C #1 binds to P2X7 receptors and this slows ATP release. ATP release is exaggerated in a spinal injury and causes cells to overwork and die, thus increasing inflammation and lengthening recovery time. Great. So this is advanced drug discussion with FD&C #1 blue as the drug. What were we talking about again?
 
bolinas said:
Basically, blue FD&C #1 binds to P2X7 receptors and this slows ATP release. ATP release is exaggerated in a spinal injury and causes cells to overwork and die, thus increasing inflammation and lengthening recovery time. Great. So this is advanced drug discussion with FD&C #1 blue as the drug. What were we talking about again?
Click to expand...

Spinal injuries don't relate to recreational drug discussion though, we don't really have a place for this kind of thread. That and all he put in OP is "random compound X binds to this receptor", no word on any sort of implications or anything like that. Much like antidepressant threads and training supplement threads, this could be advanced but in no way relates to recreational or medicinal use of CNS active drugs in its current state.

I'm trying to avoid the shit that killed mind and muscle.
 
Last edited:
^^ Thats understandable ill keep my threads more related to drug discussion from now on.
 
"no word on any sort of implications or anything like that."

Hehe i just like to get discussions going; it works depending on the state of a forum or what its about (fails currently at mind and muscle due to what its become...) but its not really related to this forum your right about that.
 
Well if you can provide a tangentially related topic to discuss such as how any CNS active drug effects it I think this would be a fine topic. Personally I'm interested in if this could be implicated in "chemobrain".
 
J Neurosci. 2010 Jun 9;30(23):8042-7.
Involvement of spinal microglial P2X7 receptor in generation of tolerance to morphine analgesia in rats.
Zhou D, Chen ML, Zhang YQ, Zhao ZQ.
Source
Unit of Pain Research, Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Abstract
Morphine loses analgesic potency after repeated administration. The underlying mechanism is not fully understood. Glia are thought to be involved in morphine tolerance, and P2X(7) purinergic receptor (P2X(7)R) has been implicated in neuron-glia communication and chronic pain. The present study demonstrated that P2X(7)R immunoreactivity was colocalized with the microglial marker OX42, but not the astrocytic marker GFAP, in the spinal cord. The protein level of spinal P2X(7)R was upregulated after chronic exposure to morphine. Intrathecal administration of Brilliant Blue G (BBG), a selective P2X(7)R inhibitor, significantly attenuated the loss of morphine analgesic potency, P2X(7)R upregulation, and microglial activation. Furthermore, RNA interference targeting the spinal P2X(7)R exhibited a similar tolerance-attenuating effect. Once morphine analgesic tolerance is established, it was no longer affected by intrathecal BBG. Together, our results suggest that spinal P2X(7)R is involved in the induction but not maintenance of morphine tolerance.
Click to expand...
Inhibition of the ATP-gated P2X7 receptor promotes axonal growth and branching in cultured hippocampal neurons.
Díaz-Hernandez M, del Puerto A, Díaz-Hernandez JI, Diez-Zaera M, Lucas JJ, Garrido JJ, Miras-Portugal MT.
Source
Departamento de Bioquímica y Biología Molecular IV, Facultad de Veterinaria, UCM, 28040-Madrid, Spain.
Abstract
During the establishment of neural circuits, the axons of neurons grow towards their target regions in response to both positive and negative stimuli. Because recent reports show that Ca2+ transients in growth cones negatively regulate axonal growth, we studied how ionotropic ATP receptors (P2X) might participate in this process. Our results show that exposing cultured hippocampal neurons to ATP induces Ca2+ transients in the distal domain of the axon and the concomitant inhibition of axonal growth. This effect is mediated by the P2X7 receptor, which is present in the growth cone of the axon. Pharmacological inhibition of P2X7 or its silencing by shRNA interference induces longer and more-branched axons, coupled with morphological changes to the growth cone. Our data suggest that these morphological changes are induced by a signalling cascade in which CaMKII and FAK activity activates PI3-kinase and modifies the activity of its downstream targets. Thus, in the absence or inactivation of P2X7 receptor, axons grow more rapidly and form more branches in cultured hippocampal neurons, indicative that ATP exerts a negative influence on axonal growth. These data suggest that P2X7 antagonists have therapeutic potential to promote axonal regeneration.
Click to expand...
Stopped being lazy and found 2 things wich possibly make the blue beaty relevant for us; inhibition of morphine tolerance and promotion of axonal regeneration (i suppose this is what ppl look for with long term drug related issues in some cases.)
 
After a several weeklong severe drugbinge 2 years ago were i was basicly overdosing all the time i was left with serotonine releasers and GHB pretty much non rewarding and with G even inducing abscence seizures straight away; either that or brainzaps.

Its most likely neurotoxic damage as this suddenly appeared in that period and no gradual tolerance was developped.

Since im a noob on "brainrecovery" could this compound be something im looking for? As i know 100 things wich are being called "neurotrophic" but what could help me?
 
Any idea of the affinity of brilliant blue G? If the dose is so high that one turns blue perhaps one should stick with ibuprofen...
 
MeDieViL said:
After a several weeklong severe drugbinge 2 years ago were i was basicly overdosing all the time i was left with serotonine releasers and GHB pretty much non rewarding and with G even inducing abscence seizures straight away; either that or brainzaps.

Its most likely neurotoxic damage as this suddenly appeared in that period and no gradual tolerance was developped.

Since im a noob on "brainrecovery" could this compound be something im looking for? As i know 100 things wich are being called "neurotrophic" but what could help me?
Click to expand...

Thanks for linking the relevant studies on this, it helps foster discussion as well as keep the board on topic (yeah, I know the antibiotic thing is a little offtopic but such a beautiful OP...).

Well it looks somewhat promising, granted I don't have a strong understanding of ATP receptors beyond their role in pain. I would hazard a guess that the dye would have a very small positive effect if it doesn't produce other side effects.

What I would more look at is the areas of the human brain most effected by MDMA (or other 5HT releasers if there are any good studies), and then do the same for GHB while checking the areas with highest GHB receptors or other relevant targets for the drugs. Might be best to start a "GHB toxicity in humans" style thread rather than focus on a single receptor target, ATP receptors are pretty much there to inform cells of their ATP reserves or if their neighboring cells are damaged to the best of my understanding.

Keep in mind your previous polydrug abuse might have caused novel kinds of damage vs what is reported in mono-drug trials.

-EA
 
You must log in or register to reply here.
Top