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

作者：Peral Assumpta; Gallar Juana; Pintor Jesus^*

来源：Experimental Eye Research, 2009, 89(1): 63-70.

DOI：10.1016/j.exer.2009.02.010

• adenine nucleotides
• glaucoma
• cholinergic nervous system
• intraocular pressure
• P2 receptors
• purinergic transmission

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 mu g/mu L) of adenine nucleotides (ATP, 2-meS-ATP, ATP-gamma-S, alpha,beta-meADP, alpha,beta-meATP and beta,gamma-meATP). Those nucleotides reducing IOP (alpha,beta-meATP and beta,gamma-meATP) were then tested in concentrations ranging from 1 to 100 mu g/mu L to obtain the IC(50) value. Several antagonists for the P2 and adenosine A1 receptors (all at 10 mu g/mu L) were assayed 30 min before the application of the hypotensive nucleotide beta,gamma-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 mu g/mu L) and parasympathetic (atropine and hexametonium at 10 mu g/mu L) receptors' antagonists were used 30 min before the instillation of beta,gamma-meATP. alpha,beta-meATP and beta,gamma-meATP decreased IOP to 60% of control value (basal IOP = 23.2 +/- 1.3 mmHg), with IC(50) of 1.59 +/- 0.21 mu g/mu L and 0.56 +/- 0.62 mu g/mu L, which corresponds to 3 mM and 1 mM respectively. Denervation completely abolished the effect of beta,gamma-meATR Sympathetic antagonists did not modify the hypotensive effect of beta,gamma-meATP, but parasympathetic antagonists were able to abolish it. Among the series of adenine nucleotide tested, alpha,beta-meATP and beta,gamma-meATP presented hypotensive actions on IOP, beta,gamma-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.

• 出版日期2009-6