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JESÚS PINTOR AN. R. ACAD. NAC. FARM.

Diadenosine polyphosphates (ApnA) present a similar behaviour

as that observed for mononucleotides. Of all the tested dinucleotides,

Ap3A and Ap4A presented a clear reduction in IOP, with the others
presenting a hypertensive effect. Ap4A was a potent agonist and
produced a decrease in intraocular pressure (29.6% of decrease), at

concentrations 3 orders of magnitude below those at which Ap2A,
Ap3A, or Ap5A produced an increase. The dose-response curve for
Ap4A did not appear to inflect at the highest concentrations tested
points at which activation of the excitatory receptor might be

expected. At the lowest concentrations tested, none of Ap2A, Ap3A,
and Ap5A produced a decrease in intraocular pressure, which implies
that in addition to there being two separate populations of receptors,

one mediating an increase and the other a decrease in intraocular

pressure, this latter receptor is specific for Ap4A. It is possible that
Ap4A also activates the excitatory receptor, but in the mixed

FIGURE 3. Effect of nucleotides reducing IOP by acting on cholinergic
terminals located in the ciliary muscle. A. Under normal conditions the
irido-corneal angle (inside the circle) permits the drainage of the aqueous humour
through the trabeculum. B. P2X receptors present in cholinergic terminals from
the parasympathetic nervous system innervating the ciliary processes can stimulate
the release of more acetylcholine (ACh). This transmitter contracts the ciliary
muscle that pulls the scleral spur opening the irido-corneal angle therefore

reducing the hydrodynamic resistance of the aqueous humour.

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