A(1)-, A(2A)- and A(3)-subtype adenosine receptors modulate intraocular pressure in the mouse

Abstract

Despite the potential importance of the mouse in studying the pharmacology of aqueous dynamics, measurement of intraocular pressure (IOP) in its very small eye has been problematic. Utilizing a novel servo-null electrophysiologic approach recently applied to the mouse, we have identified a diversity of adenosine-receptor mechanisms in modulating IOP in this species. We report the first evidence that A(3) receptors increase IOP in any species, and verify in the mouse reports with larger mammals that A(1) receptors lower and A(2A) receptors increase IOP.

Figure 1

Means±s.e.mean of the responses to minimally effective concentrations of AR agonists and antagonists: 100 nM CPA, 100 nM DCPCX, 60 μM CGS 21680, 100 nM ZM241385, 200 nM Cl-IB-MECA, 140 nM IB-MECA, 25 μM MRS 1191, 11 μM MRS 1097, and 400 μM MRS 1523. At the extreme right of the bar graph, data are presented for 100 μM adenosine with and without pretreatment with the A₃ AR antagonist MRS 1191.

Figure 2

Representative IOP tracings assessing effects of MRS 1191 and adenosine on mouse IOP. (a) MRS 1191 (25 μM) lowered baseline IOP by 2.62±0.04 mmHg, following which the response to 100 μM adenosine (+2.52±0.03 mmHg) was substantially attenuated; see, e.g., Figure 2b). (b) In the absence of the A₃ antagonist, 100 μM adenosine consistently produced several-fold larger increases in IOP, in this eye raising IOP by 31.9±0.1 mmHg.