This week in class we discussed the affect of alcohol on the brain, specifically what does ethanol start when a cell is exposed to it. As it turns out there are many different processes which alcohol sets off in the cell. First we have adenylyl cyclase activating protein kinase A. This pathway is important because it leads to the activation of many different proteins within the cell and affects everything from the reward system in the brain to the breaking down of sugar. This happens when we see ethanol blocking type I equilibrative nucleoside transporters which leads to the accumulation of adenosine on the surface of the cell. This buildup leads to the activation of A2a receptors which increases the activity of adenylyl cyclase. This process is also important because it leads into why alcohol is so addictive. PKA eventually leads to the activation of a protein called CREB which expresses, that is activates the production of, several proteins that are involved in behavioral responses to various substances. The article also talks about a protein called DARPP-32 which allows dopamine receptors to remain active although ethanol by itself would otherwise inhibit the activation of such receptors.
Another important molecule that alcohol interacts with is called Fyn kinase. Fyn kinase’s function in the cell is to phosphorylate, which means in this case activate, the NR2B subunit of the NMDA receptor which thereby increases the receptor’s function. What happens when ethanol interacts with Fyn kinase is that the ethanol causes Fyn kinase to dissociate from a protein called RACK1, the job of which is to prevent Fyn kinase from doing its job. Once dissociated, the Fyn kinase is able to activate the NR2B subunit.
Another important molecule that the researchers in our paper believed that alcohol interacts with is protein kinase C which is involved in the building up of a tolerance to alcohol and the desire for alcohol. The researchers believe that PKC is preventing the suppression of GABA-A receptors by other proteins. PKC also affects glycine receptors, but the researchers are not yet sure about the mechanism by which this is done.
The last protein which the paper focused on is that of phopholipase D. Under normal circumstance, Phospholipase D turns the phospholipids that make up the membranes of your cells into phosphatidic acid which goes on to activate other processes in the cell, the activation of protein kinase C for example. What happens when ethanol is present is that the phospholipase D has a preference for ethanol over its normal target. Phospholipase D interacts with ethanol and creates phosphatidylethanol which isn’t as good of a messenger as phosphatidic acid was. Phophatidylethanol is also thought to be a cause of the tolerance which develops for ethanol’s intoxicating effects.
In our discussion group this week I found that our groups seemed to be most interested in the question of whether alcoholism is a biological problem or an environmental problem, that is to say whether it is an individuals fault for their alcoholism, or the fact of where they grew up. Our group seemed to agree that the environment in which the person lives plays the greatest role in the development of alcohol as we actually had two group members who were able to live in a country where alcohol consumption is much higher per capita than it is in the US. They said that drinking is done much more socially, rather than to feel the effects of the alcohol as quickly as possible. They also said that alcohol is a lot less taboo and that it is more expensive in those countries. They contrasted this with our own community where we drink to get drunk and there are enough drink specials going on with enough frequency that you could get drunk every night of the week if you wanted. Anyway, I agree with the rest of the group in that we could do a lot towards decreasing alcoholism if we changed the drinking culture.