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

vesicular storage and exocytotic release of nucleotides with other
neurotransmitters is now well established, and the kinetic properties
of the granular and vesicular nucleotide transporter, exhibiting a
characteristic mnemonic regulation, have been studied by our group
(7, 8). However, the extracellular signalling mediated by ATP and
nucleotides is so broadly extended, that other mechanisms for
nucleotide release should exist. For a non-quantal, or non Ca2+
dependent exocytotic release, numerous membrane proteins have
been postulated such as some members of the ABC transporter
family, members of the ecto-ATPase family known as CD-39, or
connexins hemichannels, and constitutes a fertile area of debate and
research (9).

The physiological effects of extracellular nucleotides conclude by
the action of ectonucleotidases, rendering phosphate and the
nucleosides. The broad variety and abundance of these enzymes in
all studied cells have made difficult the study of nucleotide receptors
responses (10).

NUCLEOTIDE RECEPTOR FAMILIES

The nucleotide receptors are grouped in two big families, the
ionotropic, known as P2X, and metabotropic, called P2Y.

Metabotropic P2Y family

The metabotropic P2Y family contains 8 members, P2Y1,2,4,6,11,12,13,14
receptors. Due to their variety they are trying to divide them in three
families, essentially depending on the G protein with which they
couple preferentially, and the nature of the nucleotide agonist. This
way we have the P2YA group coupled to Gq and Gs and which prefer
adenine nucleotides (P2Y1 and P2Y11). The next group is P2YB,
coupled to Gq and Gi/o, which can recognize both uridine and
adenosine nucleotides (P2Y2, P2Y4, P2Y6). The P2YC group, couple
essentially to Gi and recognize with great efficiency ADP (P2Y12,
P2Y13), while P2Y14 is activated by UDP-glucose. Attempts to assign
other members to the P2Y family have been rejected (11). The effects

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