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

population the effects of activation of the receptor that mediates a

decrease in pressure predominated.

When investigating the place where Ap4A exert its action and in
clear contrast to what happen with mononucleotides, Ap4A facilitates
the drainage of the aqueous humour in the trabecular meshwork.

This fact leads us to hypothesize that, at least in part, the hypotensive

effect of Ap4A in eyes is mediated by an increase in aqueous outflow
(Figure 4). When instilled topically, dinucleotides are likely to

stimulate purinergic receptors present in the trabecular meshwork

to increase aqueous humour outflow as well as other purinergic

receptors present in the eye, such as those in the ciliary. Nevertheless,

the hypotensive effect of Ap4A seems to be well correlated with
the increase in outflow facility found here (44). By means of

immunocytochemical and western blot techniques we have described

the presence of P2Y1, P2Y2, and P2Y4 in bovine trabecular meshwork
cells. In contrast, the immunocytochemistry and Western blot results

seem to clearly indicate the absence of P2Y6 and P2Y11 purinoceptors.
Using the same antibodies, it was possible to identify these receptors

in rat ocular structures such as the corneal epithelium (P2Y6) and
the retinal pigmented epithelium (P2Y11) and to confirm the existence
of P2Y1 and P2Y2 in sections containing the trabecular meshwork
(44, 45). Other studies have also reported the presence of P2Y1 and
P2Y2 receptors in bovine trabecular meshwork cells (46) and P2Y1,
P2Y4, and P2Y11 in a human trabecular meshwork cell line (47).
ApnAs are known to activate several different purinergic receptors:

Ap3A and Ap4A both activate P2Y1 receptors with different selectivity,
whereas Ap5A is, in general, less effective at this receptor (48).

Furthermore, Ap4A is a good agonist at P2Y2 and P2Y4 receptors,
and although Ap3A and Ap5A can also activate these receptors,
they do so with less affinity. P2Y receptors act via a Gq/11 protein

coupling to activate PLC, IP3 formation, and mobilization of [Ca2 ]i,
although coupling to adenylyl cyclase, PLA2, PKC, NO synthase, or

BKCa channels activation has also been described (1).

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