Naked Science Forum
Life Sciences => Physiology & Medicine => Topic started by: smart on 24/06/2016 15:35:44
-
The biological mecanism of intracellular trafficking by anandamide appears not well characterized:
Does cellular uptake and diffusion (trafficking) of anandamide mediate its anti-inflammatory activity on prefrontal cortex neurons?
What is the role of fatty acid binding proteins in the organized trafficking of anandamide?
My hypothesis is that anandamide trafficking by intracellular CB1 activation may modulate the activity of the GPR55 receptor and induce neuronal differentiation in prefrontal cortex neurons.
-
Does cellular uptake and diffusion (trafficking) of anandamide mediate its antidepressant activity on prefrontal cortex neurons?
Anandamide doesn't elicit any appreciable antidepressant activity in vivo, due to its extremely short half-life, rapid hydrolysis and extensive catabolism by FAAH - which is why pharmaceutical approaches target the blockade of anandamide hydrolysis.
-
My hypothesis is that anandamide trafficking by intracellular CB1 activation may modulate the activity of the GPR55 receptor and induce neuronal differentiation in prefrontal cortex neurons.
CB1 receptors do not mediate anandamide's intracellular activity. The AEA transport system regulates uptake of anandamide from the synaptic cleft. FAAH regulates both the amplitude and duration of anandamide's biological activity.
-
Anandamide is a partial agonist of CB1 receptors in sensory neurons:
The endogenous fatty acid anandamide (AEA) is a partial agonist at cannabinoid CB1 receptors and has been reported to be a full agonist at the recombinant vanilloid receptor, VR1.
http://www.ncbi.nlm.nih.gov/pubmed/12359623
Agonist-induced internalization and trafficking of cannabinoid CB1 receptors in hippocampal neurons.
http://www.ncbi.nlm.nih.gov/pubmed/11264316
-
Anandamide is a partial agonist of CB1 receptors in sensory neurons:
The endogenous fatty acid anandamide (AEA) is a partial agonist at cannabinoid CB1 receptors and has been reported to be a full agonist at the recombinant vanilloid receptor, VR1.
http://www.ncbi.nlm.nih.gov/pubmed/12359623
In addition to it's short half-life, rapid hydrolysis and extensive catabolism by FAAH, anandamide displays extremely poor affinity to CB1 receptors - have you reviewed the Ki values?
This is precisely why methanandamide was synthesized as a pharmacologic replacement.
-
In addition to it's short half-life, rapid hydrolysis and extensive catabolism by FAAH, anandamide displays extremely poor affinity to CB1 receptors - have you reviewed the Ki values?
This is precisely why methanandamide was synthesized as a pharmacologic replacement.
Also worth noting, methanandamide activates GPR55 expression in vivo.... anandamide does not.
-
In contrast, FAAH-deletion and/or inhibition permits potent CB1-affinity by anandamide in vivo.
-
How does retrograde anandamide signaling affect FAAH metabolism?
http://www.ncbi.nlm.nih.gov/pubmed/12770562
-
How does retrograde anandamide signaling affect FAAH metabolism?
http://www.ncbi.nlm.nih.gov/pubmed/12770562
It doesn't.
Anandamide is metabolized by FAAH.
-
Anandamide is metabolized by FAAH.
Is caffeine a pharmacological FAAH inhibitor?
I'm interested in understanding how retrograde anandamide signaling is diffused via caffeine, possibly blocking FAAH activity on-demand.
-
Taken together the results demonstrate that anandamide mobilizes Ca2+ from a caffeine-sensitive intracellular Ca2+ store that functionally overlaps in part with the internal stores mobilized by histamine.
http://www.ncbi.nlm.nih.gov/pubmed/10323591
Anandamide mobilization enhance intracellular Ca2+ signaling via partial CB1 agonism.
-
Anandamide is metabolized by FAAH.
Is caffeine a pharmacological FAAH inhibitor?
I'm interested in understanding how retrograde anandamide signaling is diffused via caffeine, possibly blocking FAAH activity on-demand.
I haven't looked, but there's no way caffeine can elicit pharmacological FAAH-blockade.
-
Caffeine
Co-administering caffeine and cannabis has a long history. Bell [272] claimed that oral administration of hashish with coffee increased the effects of cannabis, and at the same time diminished its duration. He proposed a pharmacokinetic mechanism—coffee promoted more rapid absorption of hashish.
Caffeine and theophylline are antagonists of adenosine receptors. Adenosine receptors are tonically activated by adenosine, their endogenous ligand. Rodent studies indicate that A1-subtype adenosine receptors tonically inhibit CB1 activity [273]. Thus the antagonism of A1 receptors by caffeine and theophylline enhances eCB system function (e.g., activation of CB1 by 2-AG). Caffeine potentiated CB1-mediated activity stimulated by THC and WIN-55,212 in hippocampus slices [273].
Antagonism of adenosine receptors via caffeine potentiate intracellular CB1 activation: THC can stimulate caffeine effects on retrograde endocannabinoid signaling.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951193/
-
THC potentiate striatal neurotransmission via adenosine antagonism.
-
Does anandamide stimulate synaptogenesis ?