• N&PD Moderators: Skorpio | thegreenhand

Amphetamines mechanism of action

Status
Not open for further replies.

BilZ0r

Bluelight Crew
Joined
Dec 15, 2003
Messages
6,675
I uploaded a version of this Powerpoint Presentation (87k) in ED a while back, but I've tidied it up a bit, and the captions come in time now...

It's basically summing up the research done in:
Kantor L, Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME.
Protein Kinase C and Intracellular Calcium Are required for Amphetamine-Mediated Dopamine Release via the Norepinephrine Transporter in Undifferentiated PC12 Cells
J Pharmacol Exp Ther 2001 297(3):1016-1024

Giambalvo CT.
Mechanisms underlying the effects of amphetamine on particulate PKC activity.
Synapse. 2004 Feb;51(2):128-39

Khoshbouei H, Sen N, Guptaroy B, Johnson L, Lund D, Gnegy ME, Galli A, Javitch JA.
N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux.
PLoS Biol. 2004 Mar;2(3):E78
 
You sir, are an asset to the online drug community. Please, keep up the excellence.
 
Intresting, i would like to see more on such a thing for amphetamines.

That was very well done.
 
thats fantastic. I wish this sort of thing was available for more drugs.
 
physiological phosphorylation of DAT

That's nice.
any info/idea as to how/when/why DAT is phosphorylated by PKC under physiological conditions?

is there a structure out for DAT (or any of the Na+/Cl- NT transporters) yet do you know? i'll bet its got a bunch of nifty phosphorylation sites on it for different stimuli/responses.

nice to see you got your forum up and running BilZ0r

(infil from undernet)
 
Well it think its PKC phosphorylated to mediate internalization.... as far as I remember, normal substrates, favour a conformation inhibiting phosphorylation, so that when there is lots of substrate, there is little internalization, and lots of transporters to take up the monoamine... transport inhibitors block this, and thats why you get lowered transporter levels on treatments with transporter inhibitors... (1)
...I also geuss it allows for uptake control by receptors

The only 12 membrane spanning Na+ dependent transporter they have gotten the strucutre of is the bactarial NHaA transporter... from knowing its structure they geuss the DAT would look like this:
6-DAT.jpg

I believe red is negative and that is the extracellular side

From: Molecular model of the neural dopamine transporter
Aina Westrheim Ravna, Ingebrigt Sylte & Svein G. Dahl
Journal of Computer-Aided Molecular Design 17: 367–382, 2003.
 
Status
Not open for further replies.
Top