Posted by jrbecker on June 18, 2003, at 23:33:10
In reply to Re: BPD, GRK, and dopamine » jrbecker, posted by SLS on June 18, 2003, at 12:10:17
Scott,
GRK-3 activation is largely there as a control mechanism against dopamine overactivty. In one article about the recent discovery, Kelsoe made the analogy of "like being born on cocaine" when GRK-3 is not working correctly. So this speaks more to manic symptoms than it does symotoms of the depressive cycle. However, Kelsoe theorized that the likely dysfunctional GRK-3 gentic location is called the promotor region, which is responsible for turning the kinase on and off. And just like in some people, it might be more of an issue of turining it off as it is as turning it on. Thus, thsi might explain variances of individuals who are more prone to atypical-featured bipolar depression vs. classic bipolar I or frequent cycling. But I think the overall dysfunction refers to variances in consistent modulation of GRK-3. See article for more...
http://www.sciencedaily.com/releases/2003/06/030617080403.htm
I posted a link to Kelsoe's presentation in an above link (it's powerpoint) and I'll provide it again here below. There's really some great points he makes about genetic research. Most importantly, he states that there's anywhere from 20-200 major genetic defects that might predispose someone to bipolarity, so the idea of GRK-3 as the "single" defect is not at all likely. Secondly, and more interesting, he states that any genetic test can only explain 50-70% of an illness. Meaning there is still a lot of room for phenotypic (environmental) expression as well as other unknown factors. So it seems Kelsoe silences most of his doubters about this new discovery by somewhat agreeing with them in the notion that this is really only one small piece of the puzzle -- but an integral piece perhaps.A few of the slides actually go through the different chromosomes they have flagged as possibly implicated in the disease. One slide mentions all of the possible genetic links that come out of this meta-analysis, including one for brain-derived neurotrpic factor (BDNF) and another for regulation of the circadian clock (that one's definitely part of my issue!!).
http://ethics.ucsd.edu/seminars/2003/kelsoe.ppt
I"ll try to figure out if there's some way to convert the presentation from powerpoint so that everybody can view it, but I would definitely recommend trying to find a way to print this out if you can. It's fairly interesting stuff.
JB
> Hi JRB
>
> > G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity.
>
> Do you know in which direction the excitability of DA neurons is modulated by GRK-3? In other words, if the activity of GRK-3 is increased, how is DA neurotransmission influenced? Is the sensitivity or experession of DA receptors changed? Second messengers?
>
> Thanks.
>
>
> - Scott
poster:jrbecker
thread:234222
URL: http://www.dr-bob.org/babble/20030614/msgs/234974.html