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JESÚS PINTOR AN. R. ACAD. NAC. FARM.

glycoprotein P have been proposed as elements involved in the
release of nucleotides (19, 20). It has been described that ATP leaves
corneal endothelial cells by means of connexin hemichannels when
these cells are stimulated mechanically (21). We think that the latter
may be the most plausible mechanism although we cannot discard
the other previously suggested.

Since diadenosine polyphosphates are present naturally in tears,
experiments were performed in order to investigate whether the
topical application of these substances were able to change tear
production. Of all the tested dinucleotides (Ap2A-Ap6A, at 100 µM),
Ap4A, Ap5A and Ap6A were able to increase tear secretion between
20% to 60%, the best being Ap4A (Figure 1B). Some mononucleotides
also were able to increase tear production UTP and ATP being the
best ones and increasing tearing 60% and 40% respectively over the
control values (14).

FIGURE 1. Presence and effect of diadenosine polyphosphates on tear
secretion. A. The presence of diadenosine polyphosphates has been identified by
high performance liquid chromatography indicating the presence of diadenosine

triphosphate, Ap3A, diadenosine tetraphosphate, Ap4A and diadenosine
pentaphosphate, Ap5A in human tears. B. The topical application of 100 µM
of the dinucleotides produce a different behaviour on the rate of tear secretion
depending on the phosphate chain. Among all, Ap4A was able to increase tear

secretion 60% above the normal tear production.

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