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M.ª TERESA MIRAS-PORTUGAL Y COLS. ANAL. REAL ACAD. NAC. FARM.

66). The presence at the presynaptic level of a large variety of
ionotropic and metabotropic receptors suggests the possibility of
multiple interactions and cross-talk, an attempt to understand some
of them is described in next paragraph.

INTERACTION OF P2X AND OTHER IONOTROPIC AND
METABOTROPIC RECEPTORS AT THE PRESYNAPTIC

LEVEL

Ionotropic receptors interaction

Previous publications from our group reported the coexistence of
ionotropic ATP and dinucleotide receptors with neuronal nicotinic
receptors (41, 60), both being functional when are separatedly
stimulated. This fact posses a series of questions: 1) whether a
synergism between them exists, maybe leading to an exhaustion of
the terminals, 2) whether they exclude each other and to what extent,
and 3) whether their own subunits interacts with each other. This
last possibility has been outlined in an interesting work by Khakh et
al. (67), in which they show that the coexpression of ATP homomeric
P2X2 and acetylcholine receptors, nicotinic a3-ß4 in oocytes, interfere
mutually in the ion intake responses. If this happens in particular
terminals it is something important, since a3, a4 and a7 nicotinic
subunits have been involved, when they are located at a presynaptic
level, in Alzheimer’s disease, and constitute nowadays a preferential
target in the new pharmacology to alleviate said disease. This is only
an example of how complex are the interactions between different
ionotropic receptors, in which nucleotide receptors widely
participate, and that beyond this complexity it is necessary to
undertake, if we pretend to understand how is actually functioning
the presynaptic area.

The specific situation of nicotinic and nucleotidic ionotropic
receptors colocalizing at the same terminal exhibits relevant
functional characteristics, because the activation of nicotinic
receptors inhibits in a high extent the ionotropic P2X, and
dinucleotide receptors calcium responses. This reduction in the
calcium entrance also results in a decrease in the acetylcholine

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