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VOL. 72 (3), 519-538, 2006 NEW PERSPECTIVES IN OCULAR PHARMACOLOGY...

modestly contributed to the discovery of new biological molecules
and their implications in the eye physiology and physiopathology.
We have investigated the role of extracellular nucleotides and
dinucleotides in the eye. Nucleotides and dinucleotides can exert
extracellular actions by means of the activation of different
membrane receptors termed P2 purinergic receptors, which are
described in the following section.

RECEPTORS FOR EXTRACELLULAR NUCLEOTIDES

The effects of nucleotides are due to the existence of receptors
in cell membranes termed P2 receptors that transmit the message
into the cell producing certain changes in the cell biochemistry. In
this sense, nucleotides can bind and activate to two major types
of receptors, metabotropic nucleotide receptors or P2Y receptors
and ionotropic P2X receptors (1, 2). P2Y receptors are seven
transmembrane domain proteins coupled to phospholipase C via G
proteins, although some of the newly cloned P2Y receptors can
regulate adenylate cyclase and presumably can be coupled to other
second messenger system (3-5). The family of P2Y receptor is formed
by six cloned receptors termed as P2Y1, P2Y2, P2Y3, P2Y4, P2Y6 and
P2Y11, P2Y12, P2Y13, and the UDP-glucose receptor (3, 6-9). P2X
receptors are receptor-operated ion channels selective to small
cations such as Na+ and Ca2+. These receptors are involved in fast
synaptic transmission between neurones and between autonomic
nerves and smooth muscle, where ATP is the main transmitter.
Molecular biology has permitted the identification of up to seven
P2X receptors named P2X1– P2X7. It is generally accepted by the
scientific community that these receptors are formed by more than
one subunit because each subunit contains only two transmembrane
domains. The differences established between the pharmacological
experiments performed in expression systems and in native tissues
strongly suggests that P2X receptors are heteromeric rather than
homomeric receptors (for a full review, see 10).

The eye contains P2 receptors in its structures and thus it is
susceptible to be activated by the presence of nucleotides. These
changes in eye physiology can include lachrymal apparatus, cornea,

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