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(7)

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Abstract #8531 Published in IGR 5-1

Presence of diadenosine polyphosphates in the aqueous humor: their effect on intraocular pressure

Pintor J; Peral A; Pelaez T; Martin S; Hoyle CH
Journal of Pharmacology and Experimental Therapeutics 2003; 304: 342-348

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Adenine dinucleotides are present in many biological systems and may serve as physiological regulators of processes such as neurotransmitter release, vascular tone and corneal hydration. The presence of diadenosine polyphosphates was investigated in New Zealand White rabbit aqueous humor. Diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) were identified and quantified in the aqueous humor with concentrations of 0.34 ± 0.1 and 0.08 ± 0.01 μm, respectively. The effects of topical corneal application of diadenosine pyrophosphate (Ap2A), diadenosine triphosphate (Ap3A), Ap4A, and Ap5A on intraocular pressure (IOP) in rabbits were also studied. Ap2A, Ap3A, and Ap5A increased IOP with threshold doses of approximately 0.1-1.0 μg 10 μl^-1. Ap4A decreased IOP with an IC50 value of 0.12 μg 10 μl^-1 (or 0.13 nmol). Cross-desensitization studies suggested the activation of a P2X receptor for the hypotensive effect of Ap4A and a P2Y receptor in the case of Ap5A. The ATP receptor antagonists (all 100 μg 10 μl^-1), pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), suramin, and reactive blue 2 (RB-2) alone had no effect on IOP, but attenuated responses to diadenosine polyphosphates by approximately 80%. It is concluded that Ap2A, Ap3A, and Ap5A increase IOP, and Ap4A decreases IOP via mechanisms that involve P2 receptors, and that Ap4A present in aqueous humor may serve to regulate IOP. Furthermore, the authors suggest that topical application of Ap4A to the cornea has the therapeutic potential of lowering IOP, a major risk factor for glaucoma.

Dr. J. Pintor, Departamento de Bioquimica, Escuela Universitaria de Optica, Universidad Complutense de Madrid, Madrid, Spain. jpintor@vet.ucm.es

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Classification:

11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)

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