John H. John at faraway.com.au
Sun Oct 14 12:18:11 EST 2001

<dag.stenberg at nospam.helsinki.fi> wrote in message
news:9q9kv4$g0i$1 at oravannahka.helsinki.fi...
> John H. <John at faraway.com.au> wrote:
> > Dag,
> > I have evidence that NO inactivates Tryptophan hydrox ... following up
> > something on ecstasy stumbled upon this:
> >
> > The recent demonstration that TPH is inactivated by NO in vitro (Kuhn
> > Arthur, 1996, 1997) establishes the possibility that this important
> > enzyme is susceptible to inactivation by NO in vivo and could form the
> > for loss of TPH activity when NO levels are elevated in brain (e.g.,
> > amphetamine-induced).
> OK, so NO can inactivate TPH and presumably then cause depletion of 5HT,
> but how can ingestion of carbohydrates improve serotonin levels
> during continued TPH inactivation, when one would expect the
> remaining TPH to be fully saturated already?

Because the NO will only be produced during the active phases of the drug,
and while there will be low level NO occurring in some regions of the CNS in
the following few days, the amount will not be sufficient to completely
inactivate the available TPH. NO is very short lived, circa 30 secs I
believe, so by the following day ... . I believe the washout period relates
not to just diminished TPH, but a general metabolic overload that leaves a
certain amount of damage. As one of the recent ideas kicking about is that
the SSRI's achieve efficacy because the increased serotonin induces
neurogenesis (No, I don't know why this is so but others seem to be
advocating it), it would seem reasonable to assume that if people are going
to put their brains on overdrive, either through drugs or discipline, it may
help to take steps to limit the possible damage.

Another article I read on this indicated that chronic stress induces NO
throughout the cerebral cortex and impairs electron chain transport in the
process(in rats). Yet under these circumstances the TPH is not entirely
eliminated but probably is being attacked by NO to some degree. Perhaps this
is why continued stress can drive people into depression, amongst the
plethora of other possibilities, depression remaining the mystery that it

 In the previous article I cited this was also stated:

"An early manifestation of their effects[some amphets and MDMA] is a
significant inactivation of TPH (for reviews, see Gibb et al., 1993; Steele
et al., 1994; Seiden and Sabol, 1996). The mechanisms underlying these
effects on TPH are not known, but emerging data implicate drug-induced
production of reactive oxygen species (ROS) and nitric oxide (NO)."

I imagine that apart from TPH, NO is also affecting a variety of other
processes(eg Tyrosine H!).

> Dag Stenberg

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