Adenine nucleotide effect on intraocular pressure: Involvement of the parasympathetic nervous system

Nucleotides are present in the aqueous humor possibly exerting physiological effects on intraocular pressure (IOP). To determine the effect of nucleotides such as ATP and its related derivatives on IOP, New Zealand white rabbits were used. IOP was measured in rabbits treated topically either with saline (control) or with a single dose (10 μg/μL) of adenine nucleotides (ATP, 2-meS-ATP, ATP-γ-S, α,β-meADP, α,β-meATP and β,γ-meATP). Those nucleotides reducing IOP (α,β-meATP and β,γ-meATP) were then tested in concentrations ranging from 1 to 100 μg/μL to obtain the IC50 value. Several antagonists for the P2 and adenosine A1 receptors (all at 10 μg/μL) were assayed 30 min before the application of the hypotensive nucleotide β,γ-meATP. To see whether the nucleotide was acting directly on the structures involved in aqueous humor dynamics or on the autonomic nerves controlling IOP, animal denervation and sympathetic (yohimbine and ICI-118,551 at 10 μg/μL) and parasympathetic (atropine and hexametonium at 10 μg/μL) receptors' antagonists were used 30 min before the instillation of β,γ-meATP. α,β-meATP and β,γ-meATP decreased IOP to 60% of control value (basal IOP = 23.2 ± 1.3 mmHg), with IC50 of 1.59 ± 0.21 μg/μL and 0.56 ± 0.62 μg/μL, which corresponds to 3 mM and 1 mM respectively. Denervation completely abolished the effect of β,γ-meATP. Sympathetic antagonists did not modify the hypotensive effect of β,γ-meATP, but parasympathetic antagonists were able to abolish it. Among the series of adenine nucleotide tested, α,β-meATP and β,γ-meATP presented hypotensive actions on IOP. β,γ-meATP seems to stimulate cholinergic terminals being its final effect the IOP reduction. Therefore, these two nucleotides are interesting pharmacological tools for those pathologies related with high intraocular pressure.