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In conclusion, to date, two putative Arabidopsis GABA permeases have
been characterized (ProT2, AAP3). However, their affinities and speci-
ficities for GABA are relatively low. Therefore, other potential plant GABA
transporters should be explored. One promising candidate is the Arabidop-
sis homolog of the yeast GABA-specific transporter UGA4 (Fig. 12.2).
12.3
GHB, a By-Product of the GABA Shunt
and a Neurotransmitter
12.3.1
From Elixir of Life to Date-Rape Drug
GHB, a by-product of the GABA shunt (Fig. 12.1) has been at the center of
public debate since its discovery. Its structure is similar to that of GABA
(Fig.12.1)anditwas,forawhile,believedtobeawondercure,andits
purported anabolic effect of enhancing body mass prompted its use in the
fitness industry (Okun et al. 2001) until 1991, when the US Food and Drug
Administration (FDA) removed it from the market. GHB is still in use as
an adjunct to anesthesia, and induces a trancelike state that mimics sleep.
This property led to its use in sexual violence incidents in after-party hours,
where it was mixed in alcoholic beverages. As such, it gained the negative
nickname “date rape-drug” (Weir 2000).
GHB is found in all body tissues and, similar to GABA, occurs at high lev-
els in the mammalian brain where it is synthesized and stored in neurons,
and is released to the extracellular space upon Ca 2+ -dependent neuronal
depolarization. The mechanisms at the base of its proposed role as an
inhibitory neuromodulator within the central nervous system are still be-
ing evaluated. GHB has been suggested to be involved in the regulation
of GABA, dopamine (Hedou et al. 2000; Howard and Feigenbaum 1997),
5-hydroxytryptamine, acetylcholine, and serotonin metabolism (Gobaille
et al. 2002). Moreover its pharmacological actions are thought to be me-
diated through a receptor pathway mechanism, possibly by modulation of
GABA B receptors (Tunnicliff 1992; Mathivet et al. 1997; Lingenhoehl et al.
1999) as well as through specific GHB receptors (Maitre 1997; Snead 2000;
Andriamampandry et al. 2003).
TheeffectsofGHBonanimalsarediverse.GHBproducesdeepreversible
depression of cerebral metabolism, increases dopamine concentrations, in-
duces hypothermia (Maitre 1997), and decreases stroke volume and heart
rate (Mamelak 1989). A protective mechanism mediated by a GHB-induced
trancelike state has been proposed in cases of injury and hypoxia conditions
 
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