Reserpine

[BilZ0r]

"NMF" <nm_fournier at ns.sympatico.ca> wrote in
news:LvEbc.27452$j57.1390681 at news20.bellglobal.com: 

> I know of the theory that you are talking about regarding the action
> of amphetamine.  You probably know more about that literature then I
> do.  One of the problems I have had with this concept is that if the
> vesicles have become "leaky", then the vesicle must already be primed
> and partially docked at the release sites within the active zones. 
> However, those vesicles not docked would expel their content in the
> intracellular compartment and be basically catabolized by intrinsic
> enzymatic activity.  However, spontaneous transmitter release has been
> observed and this concept of already primed vesicles have also been
> experimentally verified, thus it might be possible that amphetamine
> may interact with the probability of spontaneous transmitter released
> from already primed vesicles. 

Well I think vesicles are supposed to become leaky because either a) 
amphetamines cause the monoamine transporter to work in reverse, or b) 
amphetamine increase vesicle pH, causing monoamines to dissociated from 
chaperone proteins, practically increasing the concentration of free 
amphetamine in the vesicle, which alters the equilibrium accociated with 
the monoamine transporter so that now it works in reverse.


The theory I've read about that I like that amphetamines cause calcium to 
leak from vesicles to such a degree that it causes exocytosis. At the 
same time the also do theory b) above. So you get a little bit of 
leaking, and a little bit of exocytosis.

> But can't amphetamine also intefere with the reuptake mechanism of
> various monoamines? Also doesn't amphetamine lack a hydroxyl group in
> its ring structure and possesses a isopropylamine instead of
> ethylamine side chain? I was under the assumption that these chemical
> differences from other sympathomimetic amines allowed amphetamine not
> to be destroyed by enzymes that normally affect noradrenaline?  It's
> an interesting theory, I just don't know of any evidence that
> reserpine can trigger transmitter release in a manner that you have
> asked which would be similar to amphetamine.  If you find evidence
> please post a response on it. 

There is:

Mundorf ML, Troyer KP, Hochstetler SE, Near JA, Wightman RM.
Vesicular Ca(2+) participates in the catalysis of exocytosis.
J Biol Chem. 2000 Mar 31;275(13):9136-42. 

Which is a rather horriblely presented paper, but still has some 
interesting bits in it. They used resperine to show that it decreases 
catecholamine release induced by nicotine... and if you look at the 
graph, its a histrograph of spikes per second over time... when they put 
in the resperpine, it does kinda look like it causes catecholamine 
release