TL neuro

November 13, 2011

Interesting Stuff from SfN Day 1

Filed under: Uncategorized — vapharmboy @ 9:46 pm

So, Day 1 of the SfN meeting generated some interesting news from the cannabinoid front. First off:

A. STRAIKER, K. MACKIE, J. WAGER-MILLER, T. JAIN. Both dglα and dglβ regulate the production of 2-arachidonoyl glycerol in autaptic hippocampal neurons. (38.07/D22)

The current theory is that 2-AG (one of the two endogenous cannabinoids) is generated by an enzyme called diacylglycerol lipase alpha (a.k.a., DAGL alpha, DGL-alpha, etc). Alex and his group have found evidence that another enzyme, DAGL beta, also plays an important role in 2-AG production. Unfortunately, there aren’t any currently available drugs that can tease apart the contribution of these 2 enzymes. So? Turns out that DAGL alpha deletion may be a lethal mutation. Yeah, the medicinal chemists need to get busy.

The really interesting part is that (I think) Alex (may) believe that 2-AG is also a ligand for presynaptic receptor other than CB1. Did I weaken that statement too much? Alex very circumspect about these conclusions and he clearly wants to publish their data before he makes any public pronouncements, but the prospect is enough to make a cannabi-nerd drool. The Parsimony Principle would demand that 2 distinct endocannabinoid ligands with 2 distinct synthetic pathways and 2 distinct hydrolytic pathways would only evolve if they subserved 2 distinct functions. So? Stay tuned!

And, then:

F. S. DEN BOON, Q. SCHAAFSMA-ZHAO, T. R. WERKMAN, P. CHAMEAU, C. G. KRUSE, W. VAN AKEN, W. J. WADMAN. A CB2R-mediated Ca2+-activated Cl- current contributes to the stabilization of the membrane potential of layer II/III neurons of the rat prefrontal cortex (38.08/D16)

In the good ole’ days, like before 2006, we all believed that psychoactive properties of cannabinoids were exclusively attributable to activity at CB1 receptors and the immune-modulating functions of cannabinoids were exclusively attributable to activity at CB2 receptors. Alas, the good ole’ days may be gone. There is an emerging body evidence that CB2 receptors are also found on normal (i.e., non-inflamed) neurons in the brain. Sigh.

Femke den Boon presented some data on Saturday that suggests that 1) post-synaptic CB2 receptors can be found on neurons in the medial prefrontal cortex and 2) they’re activated by drugs like JWH-133 and HU-210. Femke also thinks that these compounds may be active at intracellular (nuclear??) sites. Hmmmmmmmmmm.


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