Knockout of A3 adenosine receptors reduces mouse intraocular pressure.
OBJECTIVE
To test the putative role of A(3) adenosine receptors (ARs) in modulating intraocular pressure (IOP).


METHODS
IOP was monitored for up to 32 minutes in A3-knockout (A3AR-/-) and A3AR+/+ control mice by the servo-null approach. The IOP responses to adenosine, A3AR agonists and A3AR antagonists were studied singly or in combination in both strains.


RESULTS
IOP was significantly lower in A3AR-/- mice (12.9 +/- 0.7 mm Hg) than in A3AR+/+ control animals (17.4 +/- 0.6 mm Hg). The nonselective AR agonist adenosine produced a much smaller increase in IOP (2.2 +/- 0.8 mm Hg) in the knockout than in A3AR+/+ control mice (14.9 +/- 2.4 mm Hg). The A3-selective agonist IB-MECA did not affect IOP in A3-knockout mice, but raised it in A3AR+/+ mice. The highly selective A3AR antagonist MRS 1191 did not affect IOP in A3AR-/- mice, but lowered it in A3AR+/+ control mice. Preadministering MRS 1191 did not affect the small adenosine-triggered increase in IOP in A3AR-/- mice, but markedly attenuated adenosine's effects on IOP in A3AR+/+ control mice. MRS 1523, an A3AR antagonist less selective than MRS 1191 in rats, decreased IOP in both A3AR-/- and A3AR+/+ animals. As in black Swiss outbred mice and other mammalian species, reducing aqueous humor inflow with acetazolamide lowered IOP and administering water intraperitoneally increased IOP in both A3AR-/- and A3AR+/+ mice.


CONCLUSIONS
The reduced IOP and altered purinergic responses of IOP in A3AR knockout mice support the conclusion that A3ARs contribute to the regulation of IOP.
Department of Physiology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Marcel Y
MY
Avila
Richard A
RA
Stone
Mortimer M
MM
Civan
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000287:Administration, Topical; D000818:Animals; D004095:Dihydropyridines / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009883:Ophthalmic Solutions; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D004095:Dihydropyridines; C107728:MRS 1191; D009883:Ophthalmic Solutions; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine