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VOL. 73 (4), 1127-1157, 2007 PHYSIOLOGICAL ROLE OF EXTRACELLULAR...

Currently we can characterize the responses in specific terminals
after functional studies, using immunohistochemical techniques. The
presynaptic ionotropic nucleotide receptors are functional and very
abundant in cholinergic terminals, identified with double dye with
the vesicle acetylcholine transporter (VAT) (43), also in GABAergic
terminals characterized by the presence of the inhibitor aminoacids
transporter (VIAAT) or of the neural isoform of glutamate
descarboxylase (GAD65) (44, 45). Similar abundance of ionotropic
nucleotide receptors is observed in aminergic terminals in striatum,
characterized by the presence of monoamine vesicular transporter
(VMAT-2). We should emphasize its equally abundant presence in
glutamatergic terminals, detected by immunohistochemistry of the
vesicular glutamate transporter, both the types 1 and 2 (46, 47).

It could be thought that in an analogous way we could
characterize the terminals that store ATP and dinucleotides in their
vesicles but for the moment the nucleotide vesicular transporter has
not been cloned and only kinetically characterized (8, 48).

Immunocytochemical studies have proven that P2X subunit
distribution in synaptic terminals is notoriously different than those
present in neural soma, but for the moment it is not known how a
preferential location and distribution is accomplished, and
expression tests have not been yet made in polarized cells that
can serve as a model. In previous work from our group it has
been reported that P2X3 subunit is very abundant in CNS terminals
and that all of the synaptic terminals responding to a-ß-methylen-
ATP and ATP where afterwards immunolabeled with anti-P2X3
antibodies (49). Besides, there are terminals that respond to
nucleotides and do not present staining for this subunit. Recently we
have reported that P2X7 subunit is also present in great abundance
in CNS terminals, other authors have also found this location in
peripheral nerves (42, 50-53). More than 50% of isolated synaptic
terminals from diverse areas of central nervous system exhibit
P2X7 receptors both by immunostaining and microfluorimetric
techniques. Thus, all the signalling mediated by this receptor
acquires a special relevance in the synaptic degenerative processes
(54) and should deserve special attencion in the future. Figure 3
shows the preferential distribution of some P2X at the synaptic
terminals.

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