References

12 GABA and GHB Neurotransmitters in Plants and Animals 173
12.2
The GABA Shunt and GABA Signaling
12.2.1
Mammalian GABA Signaling
In the central nervous system of mammals GABA is the major inhibitory
neurotransmitter. GABA mediates inhibitory synaptic transmission by
binding to specialized receptors localized in presynaptic or postsynaptic
membranes. Two types of receptors exist in brain cells: ionotropic receptors
(GABAA and GABAC receptors), which are ligand-gated ion channels,
and metabotropic receptors (GABAB receptors), which are coupled to Gproteins.
GABA receptors are also expressed in nonexcitable cells in a variety
of human tissues, such as heart, liver, lung, ovary, and testis (Calver
et al. 2000). These findings imply that GABA could be a signaling molecule
not only in the brain but also in other organs. GABA receptors are also
found in lower organisms such as Caenorhabditis elegans (Richmond and
Jorgensen 1999). Thus, GABA receptors seem to be widely distributed in
diverse invertebrate and vertebrate organisms.
In addition to its neurotransmitter function in mature neurons, GABA is
involved in the development of the nervous system by promoting neuronal
migration, proliferation, and differentiation (reviewed in Owens and Kriegstein
2002). These effects are mediated by the activation of GABA receptors,
which provoke depolarization of the membrane in the immature brain,
where, in contrast to the adult brain, GABA is excitatory. Indeed, GABA
is a chemoattractant that can influence neuronal growth in vitro. During
cortical development, GABA can promote DNA synthesis and cell proliferation.
Neurons become assembled into functional networks by growing
axons and dendrites, collectively called neurites. GABA regulates neuronal
differentiation by promoting outgrowth of neurites. In conclusion, in the
mammalian brain GABA plays a major role in neural transmission and development,
and it functions through interactions with specialized receptors
and transporters.
12.2.2
GABA Signaling in Plants
In plants little is known about GABA functions despite the fact it was discovered
over half a century ago (Steward et al. 1949). It has been shown that
GABA accumulates rapidly in plant tissues exposed to a variety of stresses
including acidosis, cold, anoxia, heat, salt, and draught (reviewed by Snedden
and Fromm 1999; Kinnersley and Turano 2000). Nevertheless, recent